Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Blood glucose changes surrounding initiation of tumor-necrosis factor inhibitors and conventional disease-modifying anti-rheumatic drugs in veterans with rheumatoid arthritis

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.

The Lymphoblastoid Cell Lines of Recurrence Condyloma Acuminatum Patients Produce Lower Level of Tumor Necrosis Factor Stimulated with LPS

To study the mechanism of Condyloma acuminatum (CA) recurrence, and the association of CA recurrence with the ability of the host derived lymphoblastoid cell lines (LCL) stimulated by LPS to produce tumor necrosis factor (TNF), EBV-transformed B LCL were used as TNF producing cells The ability of LCL stimulated by LPS to produce TNF was measured by bioassay The results showed that the LCL from CA patients (including recurrent and non-recurrent CA patients) produced similar level of TNF stimulated by LPS to that of normal controls (29 54%±11 28% vs 34 31%±11 46%, P =0 1498) The LCL of CA recurrent patients produced significantly lower amount of TNF than that of non-recurrent CA patients (23 72%±7 41% vs 37 33%±11 10%, P =0 0032) Compared with the normal controls, CA recurrent patients showed a decreased ability to produce TNF (23 72%±7 41 vs 34 31%±11 46, P =0 0054), whereas CA non recurrent patients had the similar ability to the controls (37 33%±11 10 vs 34 31%±11 46, P =0 4914) It was concluded that the onset of CA was not relevant to the individual's ability to produce TNF But the recurrence of CA was associated with the ability to produce TNF It was also indicated that the TNF involved cellular immunity might play an important role in the clearance of the residual HPV by the host after treatment

Increased serum and ascitic fluid levels of soluble tumor necrosis factor-p55 in hepatocellular carcinoma patients

Objective: To explore the levels of serum and ascitic fluid soluble tumor necrosis factor receptor-p55 (sTNFR-p55) and understand their clinical implication in primary hepatocellular carcinoma (HCC) patients. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to examine the levels of sTNFR-p55 in the serum and ascitic fluid in 25 HCC patients and 25 patients with liver cirrhosis (LC). The test was also performed on the serum of 30 healthy subjects who served as control group. To assess the clinical effects of increased serum concentrations of sTNFR-p55, four parameters were analyzed by logistic regression. Results: Serum and ascitic fluid levels of sTNFR-p55 in HCC patients were significantly higher than those in LC patients and controls (P=0. 001). No significant difference was found between serum sTNFR-p55 levels in the latter 2 groups (P = 0. 19), and positive correlation between serum levels of sTNFR-p55 and that in ascitic fluid was noted in the 2 patient groups (r=1. 000, P<0. 001). Levels of the sTNFR-p55 positively correlated with TBIL and AFP in the peripheral blood of HCC patients (r=0. 524, P = 0. 01 and r=0. 234, P = 0. 03, respectively). Conclusion: Increased levels of sTNFRs-p55 in the serum and ascitic fluid could reflect the abnormal immune status of the HCC patients and may help predict the development of the tumor.

Effect of Tumor Necrosis Factor-α Antagonism in Asthma:a Meta-analysis of the Published Literature

It remains controversial whether tumor necrosis factor（TNF）-α antagonism is effective for asthma.This meta-analysis was performed to evaluate efficacy of TNF-α antagonism in treatment of patients with asthma.MEDLINE,EMBASE,LILACS,and CINAHL databases were searched for English-language studies published through January 3,2010.Randomized-controlled trials comparing TNF-α antagonism with control therapy were selected.For each report,data were extracted in relation to the outcomes analyzed：asthma exacerbation,asthma quality of life questionnaire scores,and forced expiratory volume in 1 second.Four assessable trials were identified including 641 patients with asthma.TNF-α antagonism therapy was superior to control therapy in preventing exacerbations in asthmatics [pooled odds ratio 0.52（95% confidence interval 0.29-0.88）,P=0.02]however,there was a nonsignificant reduction in asthma quality of life questionnaire scores [0.23（0 to 0.47）,P=0.05],forced expiratory volume in 1 second [0.03,（-0.14 to 0.10）,P=0.74] when analyzed using standardized mean differences.TNF-α antagonism was superior to control chemotherapy in terms of asthma exacerbation,but not asthma quality of life questionnaire scores or forced expiratory volume in 1 second.

Expression of tumor necrosis factor related apoptosis inducing ligand receptor in glioblastoma

BACKGROUND： Receptors for tumor necrosis factor related apoptosis inducing ligand （TRAIL） include death receptor 4, death receptor 5, decoy receptor 1, and decoy receptor 2. Activation of death receptor 4 and 5 selectively kills tumor cells. OBJECTIVE： To detect TRAIL receptor expression in glioblastoma by immunohistochemistry and RT-PCR, and to compare this expression to that in normal brain tissue. DESIGN： Observational analysis. SETTING： Department of Pathology, the First Affiliated Hospital of Zhengzhou University; Henan Tumor Pathology Key Laboratory. PARTICIPANTS： Twenty-five patients （17 males and 8 females） who received glioblastoma resection were selected from the Fifth Affiliated Hospital of Zhengzhou University, between September 2003 to June 2004. All glioblastoma samples were diagnosed pathologically. Twenty patients （12 males and 8 females） with craniocerebral injury who received normal brain tissue resection were selected in the same time period. There were no significant differences in sex and age between glioblastoma patients or between craniocerebral injury patients （P 〉 0.05）. All patients and appropriate relatives provided informed consent, and this study was approved by the local research ethics committee. METHODS： Polyclonal antibody against TRAIL receptors and an immunohistochemical kit （batch number： 200502） were purchased from Boster Company, Wuhan. Immunohistochemistry： Expression of death receptor 4, death receptor 5, decoy receptor l, and decoy receptor 2 were observed in both glioblastoma and normal brain tissue. The experiment was performed according to the kit instructions, and positive staining was brown-yellow. Assessment： There were no positive signals （-）; weakly positive signals, positive cells 〈 25% （＋）; weakly positive signals, positive cells 25%-50% （＋＋）; strongly positive signals, positive cells 50%-75% （＋＋＋）; strongly positive signals, positive cells 〉 75% （＋＋＋＋）. Evaluation： Expression levels of TRAIL receptors were estimated in both normal brain tissue and glioblastoma. Expression of decoy receptor 1 and decoy receptor 2 mRNA in glioblastoma were detected by reverse transcription polymerase chain reaction, and expression of decoy receptor in glioblastoma was estimated. MAIN OUTCOME MEASURES： Comparison of death receptor and decoy receptor protein expression between glioblastoma and normal brain tissue; decoy receptor mRNA expression in glioblastoma. RESULTS： Death receptor protein expression was strongly positive （＋＋＋） in glioblastoma, while it was weakly positive （＋, ＋＋） in normal brain tissue. Therefore, expression rate of death receptor protein in the glioblastoma was significantly higher than that in the normal brain tissue （.~ 2 = 18.48, 23.03, P 〈 0.01）. Decoy receptor protein expression in the glioblastoma was significantly lower than that in the normal brain tissue （ x2 = 6.65, 18.76, P 〈 0.01）. The level of decoy receptor mRNA expression in glioblastoma was significantly higher than those of protein expression （ x 2 = 9.82, 10.09, P〈 0.01）. CONCLUSION： High expression of death receptor and low expression of decoy receptor are frequently observed in glioblastoma, suggesting that TRAIL receptor genes show an anti-tumor and expressive response during the initiation and development of the tumor. There are significant differences in decoy receptor expression between normal brain tissue and glioblastoma, suggesting that the restricted expression of decoy receptor in glioblastoma is regulated at the post-transcriptional level.

The interleukin-1 receptor antagonist (IL-1-Ra) and soluble tumor necrosis factor receptor I (sTNF RI) in periodontal disease

The course and severity of periodontitis can be significantly affected by bacterial virulence as well as host immunity dysfunction. Periodontal tissue destruction has been proved to result from cascade of cytokines synthesized by reactive cells upon stimulation by pathogenic bacteria and lipopolysaccharides within their cell membranes. The clinical use of genetically programmed cells, producing substances blocking IL-1, based on recombinant IL-1 antagonist, as well as cytokines activating fibroblasts and osteoblasts to regenerate the destroyed periodontal tissue could prove alternative to the conventional treatment. Another cytokine of interest in respect to periodontitis ethiopathogenesis is soluble tumor necrosis factor receptor I (sTNF RI). Observation of soluble TNF receptors as physiologic inhibitors of TNF led to its administration in therapeutic process as well as in therapy selected cases of aggressive periodontitis.

Effects of liraglutide on soluble tumor necrosis factor receptor in patients with diabetic nephropathy

Objective:To observe the effects of Liraglutide combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic nephropathy.Methods: A total of 110 patients with early diabetic nephropathy who had been seeking treatment in the hospital between December 2016 and December 2017 were selected and according to the random number table method, these patients were randomly divided into two groups, with 55 cases in each group. Patients in the control group were given conventional symptomatic treatment such as hypoglycemic therapy, whereas the observation group was treated with Liraglutide based on the conventional symptomatic treatment given to the control group. The renal function, blood glucose metabolism level, serum indexes, vascular endothelial function and adverse drug reactions were compared between the two groups.Results: After treatment, the levels of 24 hUpor, UAER and Scr in the two groups were both shown to be lower than those before treatment, and the levels in the observation group were shown to be lower than those in the control group, with the differences being statistically significant. After treatment, the levels of PBG, FPG, HOMA-IR , HbA1c and FIns in the two groups were both significantly lower than before treatment, and the levels of PBG, FPG, HOMA-IR , HbA1c and FIns in the observation group were shown to be lower than those in the control group, where the differences were statistically significant. After treatment, the levels of TNF-α, sTNFR1 and hs-CRP in the two groups were significantly reduced than before treatment, and the levels in the observation group were shown to be significantly lower than the control group, with statistically significant differences. After treatment, the NO levels in both groups were significantly increased and ET-1 level significantly reduced than before treatment, and the NO level in the observation group was shown to be higher and the ET-1 level lower than the control group, where the difference was statistically significant.Conclusion: Liraglutide is with higher safety for patients with diabetic nephropathy, which can effectively improve their renal function and blood glucose, enhance insulin sensitivity, reduce the levels of inflammatory factors, and improve the endothelial function.

Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. rmhTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00±9.92 in the trial group, and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. Conclusion: The administration of rmhTNF in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.

Effects of hemoperfusion combined with sequential dialysis on soluble tumor necrosis factor receptor in patients with diabetic kidney disease

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.

Effects of increased human tumor necrosis factor-like molecule 1A expression in peripheral blood of children with acute Guillain-Barre syndrome on interferon-gamma secretion

BACKGROUND： Human tumor necrosis factor-like molecule 1A （hTL1A） is a strong T helper cell type 1 （Thl） co-stimulator. Guillain-Barre syndrome （GBS） is an autoimmune disorder of the nervous system, which is mediated by Thl cells. OBJECTIVE： To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ. DESIGN, TIME AND SETTING： A randomized, controlled, neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University, China from November 2005 to November 2007. MATERIALS： Venous blood samples were obtained from 6 healthy donors, aged 6-12 years （all routine blood examination items were normal）, and 6 additional children with acute GBS, aged 6-12 years. The GBS children fell ill within 1 week and were not treated with hormones or immunoglobulin Purified recombinant human soluble tumor necrosis factor-like molecule 1A （rhsTL1A, 1 mg/mL, relative molecular mass 22 000, 6× His tag, soluble form） was supplied by the Central Laboratory of First Hospital of Jilin University, China. METHODS： Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates. The cells were assigned to the following groups： control （2 μg/mL phytohemagglutinin）, 2μg/mL phytohemagglutinin ＋ 25, 100 and 400 ng/mL rhsTL1A. T cell proliferation was quantified using the tritiated thymidine （3H-TdR） method. Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay （ELISA）. The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry. Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin, the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTLIA. Finally, peripheral blood mononuclear cell-secreted interferon-γlevels were measured by ELISA. MAIN OUTCOME MEASURES： The following parameters were measured： rhsTLIA stimulation index to stimulate proliferation of T cells; the serum interferon-γ levels in acute GBS children; the ratio of hTL1A-positive cells to CD3-positive cells; the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children, as well as rhsTL1A-stimulated interferon-γ levels. RESULTS： T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group. The stimulation index of the 400 ng/mL rhsTL1A group was the greatest. Serum interferon-γ levels in acute GBS children were significantly greater than the control group （P 〈 0.05）. The ratio of hTLIA＋ CD3＋ T cells to CD3＋ T cells in acute GBS children was significantly greater than the control group （P 〈 0.01 ）. Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group, and the secreted interferon-γ levels were significantly increased （P 〈 0.05）. CONCLUSION： In T cells pre-activated with 2 μg/mL phytohemagglutinin, proliferation was effectively increased with 400 ng/mL rhsTL1A treatment. Expression of hTLIA was increased in activated T cells from peripheral blood of acute GBS children, followed by increased interferon-γ secretion. These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.

Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor α mRNA in isolated rat intrahepatic bile duct epithelial cells *

AIM To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor α mRNA (TNF α mRNA) with cultured rat intrahepatic bile duct epithelial cells.

Relationship between tumor necrosis factor-α and liver fibrosis

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Influence of granulocyte-macrophage colonystimulating factor and tumor necrosis factor on anti-hepatoma activities of human dendritic cells

INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly

The Change of Interleukin-6 and Tumor Necrosis Factor in Patients with Obstructive Sleep Apnea Syndrome

The levels of lipopolysaccharide (LPS) induced interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL 6 and TNF α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL 6 or TNF α expression studied. Both IL 6 and TNF α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS induced IL 6 (787.82±151.97 pg/ml) and TNF α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL 6 (50.67±4.70 pg/ml) and TNF α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma: 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL 6 and TNF α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO 2 below 90 % in the total sleep time. It was concluded that LPS induced IL 6 and TNF α levels as well as plasma IL 6 and TNF α levels in the patients with OSAS were up regulated, which may be associated with the pathogenesis of OSAS.

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).

Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells

AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-&#x003b1;)-induced gene expression in human gastric adenocarcinoma cells.

Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

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.

Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy.