Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improv...Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.展开更多
Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumo...Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.展开更多
Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential a...Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.展开更多
AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VAR...AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.展开更多
BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine.AIM To identify predictors of long-term mucosal healing(MH) in patients with Crohn's disease(CD) treated with t...BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine.AIM To identify predictors of long-term mucosal healing(MH) in patients with Crohn's disease(CD) treated with tumor necrosis factor α(TNF-α) inhibitors.METHODS Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity(CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response(ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments.RESULTS Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment(53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52%and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46(59% sensitivity and 91% specificity; area under the curve =0.778).CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-αinhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-αtherapy.展开更多
As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The function...As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.展开更多
Objective: To observe the effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease. Methods:A total of 100 patients with diabetic ki...Objective: To observe the effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease. Methods:A total of 100 patients with diabetic kidney disease who had been seeking treatment in the hospital between May 2015 and July 2017 were selected, and then according to the random number table method, these patients were divided into a control group and an observation group, with 50 cases in each group. The control group was treated with hemodialysis only, whereas the observation group was given hemoperfusion combined with sequential dialysis for treatment. The changes of soluble tumor necrosis factor receptor, oxidant factor and metabolic indexes after 12 weeks of treatment were compared between the two groups. Results: After treatment, the metabolic indexes in the observation group were shown to be lower than the control group, the levels of soluble tumor necrosis factor receptor related indexes in the former group were lower than the control group, and the level of oxidative stress indicators in the former group was shown to be better than the control group, where the differences were statistically significant. Conclusion: For patients with diabetic kidney disease, hemoperfusion combined with sequential dialysis is with significant clinical curative effects, which can effectively relieve their oxidative stress, better control the blood glucose level, significantly improve their renal function and significantly reduce the level of soluble tumor necrosis factor receptor.展开更多
AIM To investigate the association of tumor necrosis factor alpha(TNFα)-G308 A polymorphism with different liver pathological changes in treatment-na?ve Egyptian patients infected with hepatitis C virus(HCV) genotype...AIM To investigate the association of tumor necrosis factor alpha(TNFα)-G308 A polymorphism with different liver pathological changes in treatment-na?ve Egyptian patients infected with hepatitis C virus(HCV) genotype 4.METHODS This study included 180 subjects,composed of 120 treatment-na?ve chronic HCV patients with different fibrosis grades(F0-F4) and 60 healthy controls. The TNFα-G308 A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα-G308 A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.RESULTS Current data showed that the TNFα-G308 A SNP frequency was significantly different between controls and HCV infected patients(P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients(F2-F4,n = 60) than in early fibrosis patients(F0-F1,n = 60)(P = 0.05,0.04 respectively). Moreover,the GA or AA genotypes increased the TNFα serum level greater than the GG genotype(P = 0.002). The results showed a clear association between severe liver pathological conditions(inflammation,steatosis and fibrosis) and(GA + AA) genotypes(P = 0.035,0.03,0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes(GA + AA) were significantly associated with liver inflammation(OR = 3.776,95%CI: 1.399-10.194,P = 0.009),severe steatosis(OR = 4.49,95%CI: 1.441-14.0,P = 0.010) and fibrosis progression(OR = 2.84,95%CI: 1.080-7.472,P = 0.034). Also,the A allele was an independent risk factor for liver inflammation(P = 0.003),steatosis(P = 0.003) and fibrosis(P = 0.014). CONCLUSION TNFα SNP at nucleotide-308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected展开更多
AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral center.METHODS:All patients with a confirmed diagnosis of ulcerative co...AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral center.METHODS:All patients with a confirmed diagnosis of ulcerative colitis undergoing therapy with infliximab and/or adalimumab at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between January 2011 and February 2014 were retrospectively enrolled.Patients with a followup period of less than 6 mo from start of anti-TNFα therapy were excluded.Medical records of all eligible individuals were carefully reviewed.Steroid-free clinical remission of a duration of at least 3 mo,colectomy rate,duration of anti-TNFα therapy,need for anti-TNFα dose escalation,and the occurrence of adverse events were evaluated as the main outcome parameters.RESULTS:Seventy-two patients were included(35 treated with infliximab,17 with adalimumab,20 with both consecutively).Median follow-up was 27 mo(range:6-87 mo).Steroid-free clinical remission was achieved by 22.2% of the patients(median duration:21 mo until end of follow-up; range:3-66 mo).Patients attaining steroid-free clinical remission displayed lower hemoglobin and albumin blood levels at the start of treatment than those who did not achieve remission.The overall colectomy rate was 20.8%.Nearly 50% of the patients underwent anti-TNFα dose escalation during the follow-up period.For both the infliximab and the adalimumab treated patients,non-response to anti-TNFα therapy was the major reason for treatment discontinuation.18.2% of the infliximab-treated patients and 13.5% of the adalimumab-treated patients had to discontinue their therapy due to adverse events.CONCLUSION:Real-life remission rates of ulcerative colitis under anti-TNFα are overall low,but some patients have a clear long-term benefit.展开更多
Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falcip...Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falciparum were included in this study as patients.Thirty healthy individuals of comparable age,racial and body mass index were taken as controls.All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film.Estimation of liver function test,kidney function test,complete blood count,fasting blood sugar,fasting serum insulin,pro-inflammatory cytokine tumor necrosis factor alpha(TNFα)and interleukin 1(IL1),estimation of morning serum leptin and calculation of body mass index(kg/m^2)were done in both groups on the day of admission,on discharge and 7 d after discharge.Results:At admission,leptin levels were significantly higher in patients group than in control while lasting serum insulin levels were not significantly different between the two groups.There were significant increases as regard to TNFαand IL1 in malaria patients.Significant differences were observed between the control and the patient group for leptin,TNFαand IL1 at the time of admission and discharge.After discharge for 7 d.a significant decline in scrum leptin levels,TNFαand IL1 in the patients group was observed as compared with time of admission and time of discharge,a positive correlation between serum leptin levels and TNFαand IL1.Conclusions:Leptin hormone level might play an important role in development and outcome of malaria infection.展开更多
Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necros...Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.展开更多
Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and ...Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.展开更多
The effects of tumor necrosis factor-α(TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma,were injec...The effects of tumor necrosis factor-α(TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma,were injected intraperitoneally with recombinant human TNF at a dose of 4-75×106 U/kg for 3 consecutive days.Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control.TNF resulted in significant decrease in tumor Protein fractional synthesis rate, Protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and GI phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.展开更多
BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Unders...BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.展开更多
The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied....The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80 or 160 mg kg was given ip twice every 4 day. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 hrs to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbence assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on day 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between them, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.展开更多
Aim: To study the roles of tumor necrosis factor alpha (TNF-α) on the sperm acrosin activity and acrosome reaction. Methods: The sperm acrosin activity was tested by the method of BAEE/ ADH Unity and the acrosome rea...Aim: To study the roles of tumor necrosis factor alpha (TNF-α) on the sperm acrosin activity and acrosome reaction. Methods: The sperm acrosin activity was tested by the method of BAEE/ ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-α decreased the sperm acrosin activity and acrosome reaction (P<0.01; P<0.01, respectively); it also inhibited the Ca2+-ATPase activity and SOD activity in sperm (P< 0.05; P<0.001, respectively), but increased the NOS activity and the amount of NO in sperm (P<0.001; P<0.001, respectively). While it had a less significant effect on the activity of Na+-K+-ATPase (P>0.05). Conclusion: TNF-α inhibits the sperm acrosin activity and acrosome reaction.展开更多
Objective To evaluate the effect of lamivudine on immunity of chronic hepatitis B by observing the sequential changes of serum TNF-α and HBV-DNA level. Methods 31 CHB patients with elevated serum ALT/AST level and HB...Objective To evaluate the effect of lamivudine on immunity of chronic hepatitis B by observing the sequential changes of serum TNF-α and HBV-DNA level. Methods 31 CHB patients with elevated serum ALT/AST level and HBVDNA level higher than 106 copies/mL were treated with lamivudine (100mg/day) for one year. The sequential serum samples, which were taken at the 0, 3 rd, 6 th, 12 th month after initiation of therapy, were used to detect serum level of TNF-α and quantity of HBV-DNA respectively. Results ① The serum TNF-α levels were higher than normal value before treatment in all patients; ② At In the 3 rd month of treatment, The the serum HBV-DNA level began to decline and became negative in the 54.9% of all patients. At the end of treatment, HBV-DNA was negative in 48.4% of all patients; ③ The decrease of TNF-α level was later than HBVDNA level drop. TNF-α level began to decline after 6 months treatment. At the end of treatment, TNF-α level was lower than that at in 6 th month, TNF-α level returned to normal in the 38.7% of all patients; ④ The TNF-α level decreased significantly after 6 months treatment in the patients with ALT>80IU/L at the beginning of treatment. But in the patients with ALT≤80IU/L, the TNF-α level decreased just after 12 months treatment; ⑤ TNF-α level fell obviously and early in patients whose HBVDNA became negative at in the 3 rd month. Conclusion Lamivudine can suppress the replication of HBVDNA quickly, and decrease TNF-α level in the serum TNF-α level. It suggests that lamivudine can modulate immune response directly or indirectly. The changes of serum TNF-α level may be used to evaluate the clinical efficacy of lamivudine.展开更多
文摘Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.
基金This research was funded by Guangzhou Science and Technology Plan Projects(No.202002020066)the Young Scientists to the NSFC Application of Guangdong Provincial People’s Hospital(No.8210120306)the Open Foundation of the State Key Laboratory of Bioactive Seaweed Substance(No.SKL-BMSG2022-03)。
文摘Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.
文摘Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.
基金Supported by VA HSR&D MERIT Award IIR,No.14-048-3 for Dr Caplansupported by a VA GME Enhancement Award
文摘AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
基金Supported by the Leona M.and Harry B Helmsley Charitable Trust,No.2015PG-IBD005
文摘BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine.AIM To identify predictors of long-term mucosal healing(MH) in patients with Crohn's disease(CD) treated with tumor necrosis factor α(TNF-α) inhibitors.METHODS Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity(CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response(ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments.RESULTS Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment(53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52%and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46(59% sensitivity and 91% specificity; area under the curve =0.778).CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-αinhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-αtherapy.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.31101891)the Hitech Research and Development Program of China(No.2012AA10A408)
文摘As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.
文摘Objective: To observe the effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease. Methods:A total of 100 patients with diabetic kidney disease who had been seeking treatment in the hospital between May 2015 and July 2017 were selected, and then according to the random number table method, these patients were divided into a control group and an observation group, with 50 cases in each group. The control group was treated with hemodialysis only, whereas the observation group was given hemoperfusion combined with sequential dialysis for treatment. The changes of soluble tumor necrosis factor receptor, oxidant factor and metabolic indexes after 12 weeks of treatment were compared between the two groups. Results: After treatment, the metabolic indexes in the observation group were shown to be lower than the control group, the levels of soluble tumor necrosis factor receptor related indexes in the former group were lower than the control group, and the level of oxidative stress indicators in the former group was shown to be better than the control group, where the differences were statistically significant. Conclusion: For patients with diabetic kidney disease, hemoperfusion combined with sequential dialysis is with significant clinical curative effects, which can effectively relieve their oxidative stress, better control the blood glucose level, significantly improve their renal function and significantly reduce the level of soluble tumor necrosis factor receptor.
文摘AIM To investigate the association of tumor necrosis factor alpha(TNFα)-G308 A polymorphism with different liver pathological changes in treatment-na?ve Egyptian patients infected with hepatitis C virus(HCV) genotype 4.METHODS This study included 180 subjects,composed of 120 treatment-na?ve chronic HCV patients with different fibrosis grades(F0-F4) and 60 healthy controls. The TNFα-G308 A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα-G308 A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.RESULTS Current data showed that the TNFα-G308 A SNP frequency was significantly different between controls and HCV infected patients(P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients(F2-F4,n = 60) than in early fibrosis patients(F0-F1,n = 60)(P = 0.05,0.04 respectively). Moreover,the GA or AA genotypes increased the TNFα serum level greater than the GG genotype(P = 0.002). The results showed a clear association between severe liver pathological conditions(inflammation,steatosis and fibrosis) and(GA + AA) genotypes(P = 0.035,0.03,0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes(GA + AA) were significantly associated with liver inflammation(OR = 3.776,95%CI: 1.399-10.194,P = 0.009),severe steatosis(OR = 4.49,95%CI: 1.441-14.0,P = 0.010) and fibrosis progression(OR = 2.84,95%CI: 1.080-7.472,P = 0.034). Also,the A allele was an independent risk factor for liver inflammation(P = 0.003),steatosis(P = 0.003) and fibrosis(P = 0.014). CONCLUSION TNFα SNP at nucleotide-308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected
文摘AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral center.METHODS:All patients with a confirmed diagnosis of ulcerative colitis undergoing therapy with infliximab and/or adalimumab at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between January 2011 and February 2014 were retrospectively enrolled.Patients with a followup period of less than 6 mo from start of anti-TNFα therapy were excluded.Medical records of all eligible individuals were carefully reviewed.Steroid-free clinical remission of a duration of at least 3 mo,colectomy rate,duration of anti-TNFα therapy,need for anti-TNFα dose escalation,and the occurrence of adverse events were evaluated as the main outcome parameters.RESULTS:Seventy-two patients were included(35 treated with infliximab,17 with adalimumab,20 with both consecutively).Median follow-up was 27 mo(range:6-87 mo).Steroid-free clinical remission was achieved by 22.2% of the patients(median duration:21 mo until end of follow-up; range:3-66 mo).Patients attaining steroid-free clinical remission displayed lower hemoglobin and albumin blood levels at the start of treatment than those who did not achieve remission.The overall colectomy rate was 20.8%.Nearly 50% of the patients underwent anti-TNFα dose escalation during the follow-up period.For both the infliximab and the adalimumab treated patients,non-response to anti-TNFα therapy was the major reason for treatment discontinuation.18.2% of the infliximab-treated patients and 13.5% of the adalimumab-treated patients had to discontinue their therapy due to adverse events.CONCLUSION:Real-life remission rates of ulcerative colitis under anti-TNFα are overall low,but some patients have a clear long-term benefit.
基金supported by College of Health Sciences(Grant No,HS-10-01)
文摘Objective:To analyze scrum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.Methods:Sixty cases of malaria falciparum were included in this study as patients.Thirty healthy individuals of comparable age,racial and body mass index were taken as controls.All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film.Estimation of liver function test,kidney function test,complete blood count,fasting blood sugar,fasting serum insulin,pro-inflammatory cytokine tumor necrosis factor alpha(TNFα)and interleukin 1(IL1),estimation of morning serum leptin and calculation of body mass index(kg/m^2)were done in both groups on the day of admission,on discharge and 7 d after discharge.Results:At admission,leptin levels were significantly higher in patients group than in control while lasting serum insulin levels were not significantly different between the two groups.There were significant increases as regard to TNFαand IL1 in malaria patients.Significant differences were observed between the control and the patient group for leptin,TNFαand IL1 at the time of admission and discharge.After discharge for 7 d.a significant decline in scrum leptin levels,TNFαand IL1 in the patients group was observed as compared with time of admission and time of discharge,a positive correlation between serum leptin levels and TNFαand IL1.Conclusions:Leptin hormone level might play an important role in development and outcome of malaria infection.
文摘Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.
基金This work was supported by the China Postdoctoral Science Foundation under grant No.2004035588.
文摘Tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared (IR) spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope (SEM). The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope (TEM) and fluorescence active cell sorter (FACS). The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.
文摘The effects of tumor necrosis factor-α(TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma,were injected intraperitoneally with recombinant human TNF at a dose of 4-75×106 U/kg for 3 consecutive days.Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control.TNF resulted in significant decrease in tumor Protein fractional synthesis rate, Protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and GI phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.
基金Supported by the Swiss National Science Foundation,No.P2SKP3_158649,No.P3400PB_171581,and No.P3P3PB_171582(to Bluemel S)NIH grants(in part),No.R01 AA24726,No.U01 AA026939,and services provided by P30 DK120515(to Schnabl B).
文摘BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.
文摘The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80 or 160 mg kg was given ip twice every 4 day. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 hrs to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbence assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on day 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between them, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.
文摘Aim: To study the roles of tumor necrosis factor alpha (TNF-α) on the sperm acrosin activity and acrosome reaction. Methods: The sperm acrosin activity was tested by the method of BAEE/ ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-α decreased the sperm acrosin activity and acrosome reaction (P<0.01; P<0.01, respectively); it also inhibited the Ca2+-ATPase activity and SOD activity in sperm (P< 0.05; P<0.001, respectively), but increased the NOS activity and the amount of NO in sperm (P<0.001; P<0.001, respectively). While it had a less significant effect on the activity of Na+-K+-ATPase (P>0.05). Conclusion: TNF-α inhibits the sperm acrosin activity and acrosome reaction.
文摘Objective To evaluate the effect of lamivudine on immunity of chronic hepatitis B by observing the sequential changes of serum TNF-α and HBV-DNA level. Methods 31 CHB patients with elevated serum ALT/AST level and HBVDNA level higher than 106 copies/mL were treated with lamivudine (100mg/day) for one year. The sequential serum samples, which were taken at the 0, 3 rd, 6 th, 12 th month after initiation of therapy, were used to detect serum level of TNF-α and quantity of HBV-DNA respectively. Results ① The serum TNF-α levels were higher than normal value before treatment in all patients; ② At In the 3 rd month of treatment, The the serum HBV-DNA level began to decline and became negative in the 54.9% of all patients. At the end of treatment, HBV-DNA was negative in 48.4% of all patients; ③ The decrease of TNF-α level was later than HBVDNA level drop. TNF-α level began to decline after 6 months treatment. At the end of treatment, TNF-α level was lower than that at in 6 th month, TNF-α level returned to normal in the 38.7% of all patients; ④ The TNF-α level decreased significantly after 6 months treatment in the patients with ALT>80IU/L at the beginning of treatment. But in the patients with ALT≤80IU/L, the TNF-α level decreased just after 12 months treatment; ⑤ TNF-α level fell obviously and early in patients whose HBVDNA became negative at in the 3 rd month. Conclusion Lamivudine can suppress the replication of HBVDNA quickly, and decrease TNF-α level in the serum TNF-α level. It suggests that lamivudine can modulate immune response directly or indirectly. The changes of serum TNF-α level may be used to evaluate the clinical efficacy of lamivudine.