Anti-tumour necrosis factor agent and liver injury:literature review,recommendations for management

Abnormalities in liver function tests,including transient and self-limiting hypertransaminasemia,cholestatic disease and hepatitis,can develop during treatment with anti-tumour-necrosis-factor(TNF)therapy.The optimal management of liver injury related to antiTNF therapy is still a matter of debate.Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than5 times the upper limit of normal,or the occurrence of jaundice,there are no standard guidelines for the management of anti-TNF-related liver injury.Bibliographical searches were performed in Pub Med,using the following key words:inflammatory bowel disease(IBD);TNF inhibitors;hypertransaminasemia;drugrelated liver injury;infliximab.According to published data,elevation of transaminases in patients with IBD treated with anti-TNF is a common finding,but resolution appears to be the usual outcome.Anti-TNF agents seem to be safe with a low risk of causing severe drugrelated liver injury.According to our centre experience,we found that hypertransaminasemia was a common,mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses.An algorithm for the management of liver impairment occurring during antiTNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases.However,hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.

Nitric oxide and tumour necrosis factor alpha in the process of pseudoexfoliation glaucoma

AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level.RESULTSAqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients.CONCLUSIONReduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.

AN EXPERIMENTAL STUDY OF THE TUMOUR NECROSIS FACTOR LEVELSIN AQUEOUS HUMOR AFTER TRAUMATIC CATARACT AND INTRAOCULAR LENS IMPLANTATION

Purpose. This paper studies the tumour necrosis factor (TNF) levels in aqueous humor after traumatic cataract extraction and posterior chamber (PC) intraocular lens (IOL) implantation in rabbits,and discusses the effect of TNF on postoperative anterior ocular inflammation. Methods. Twenty seven pigmented rabbits were divided into three groups: for the first group, the IOL were placed in the capsular bag after traumatic cataract extraction; for the second, the Extracapsular cataract extraction without IOL implantation; and for the third, the control group without surgical intervention. On the 1st, 3rd, 7th and 14th day postoperatively, aqueous humor samples were obtained. A modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were studied by means of analysis of variance in SAS software. Result. The TNF level was increased in aqueous humor and reached its maximum on the 1st postoperative days after traumatic cataract extraction and PC IOLs implantation, and the TNF levels are significantly higher (P<0 05) on the 1st, 3rd, 7th and 14th day postoperatively in traumatic cataract extraction and PC IOL implanted group than that in the non surgical intervention group and extracapsular cataract extraction group. Conclusions. The increase of TNF levels had a close relationship with presence of the IOL itself which induces the secretion of TNF. This suggested that TNF as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after traumatic cataract extraction and IOL implantation.

Zinc-α2-glycoprotein 1 attenuates non-alcoholic fatty liver disease by negatively regulating tumour necrosis factor-α

BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.

Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease

Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.

Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-a, but not interleukin-6,in anaesthetised rats

This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and interleukin（IL）-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli（Ec-LPS） on IL-6 and TNF-a levels were also analysed. Pg-LPS（1 mg/1 m L） or Ec-LPS（1 or 6 mg/1 m L） was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay（ELISA） revealed that gingival dialysates contained approximately 389 pg？m L21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction（RT-PCR） analysis revealed that the gingiva expresses Toll-like receptor（TLR） 2 and TLR4 m RNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.

An Experimental Study of the Tumour Necrosis Factor Level in Aqueous Humor after Transscleral Fixation of Intraocular Lens

Purpose: The tumour necrosis factor (TNF) level in aqueous humor after transscleral fixation of intraocular lens (IOL) implantation in rabbits and discuss the effect of TNF on postoperative anterior ocular inflammation.Methods: Twenty - seven pigmented rabbits were divided into three groups. Group 1: transscleral fixation of posterior chamber (PC) IOL implantation;Group 2; Lens of rabbits was removed without IOL implantation; Group 3; the comtrol group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days,aqueous humor samples were obtained. An modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were analyzed by using analysis of variance of SAS software. Results: It was found that TNF level in aqueous humor was increased after transscleral fixation of IOL implantation. TNF level reached its maximum on the 14th postoperative day in the IOL implanted group. TNF level on 1st, 3rd, 7th and 14th days postoperatively was

Tumor necrosis factor-alpha(TNF-α) in spotted halibut Verasper variegatus at the embryonic and metamorphic stages

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.

Effects of propofol on Bax and Bcl-2 expression induced by tumour necrosis factor-α in mouse spinal cord neurons in vitro

Objective:To study the effects of propofol on Bax and Bcl-2 expression induced by tumour necrosis factor-α(TNF-α) in mouse spinal cord neurons in vitro. Methods:Spinal cord neurons were isolated from fetal mice and cultured in Neurobasal medium with B27 supplement. On the 7^th day, cultured neurons were randomly divided into 6 groups: control group, propofol (50 umol/L)group, TNF-α group, propofol (25 umol/L) with TNF-α group, propofol (50 umol/ L) with TNF-α group, and propofol ( 100 umol/L)with TNF-α group. Propofol was added to the cultured cells respectively and the cells were incubated for 30 min. Then TNF-α was added to the cultured cells(the final concentration of TNF-α was 2 000 U/ml) and incubated for 24 h. The Bax and Bcl-2 expression were measured by immunocytochemical technique. Results:In TNF-α group, the expression of Eax increased and the expression of Bcl-2 decreased (P<0.01, vs control). However, treatment with various concentrations of propofol (25, 50, 100 umol/L) decreased the expression of Bax and increased the expression of Bcl-2 (P<0.05, P<0.05, P<0.05, vs TNF-α). Conclusion: Propofol can inhibit the apoptosis induced by TNF-α by modulating the expression of Bax and Bcl-2.

Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer

Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.

Effects of Tryptergium Wilfordii Polyglyco-sidium on the Tumour Necrosis Factor Levels in Aqueous Humor after Intraocular Lens Implantation

Purpose : Effects of Tryptergium Wilfordii Polyglycosidium (TWP) on the Tumour Necrosis Factor (TNF) levels in aqueous humor after intraocular lens (IOL) implantation were studied in rabbits.Methods: Twenty-seven pigmented rabbits were divided into three groups. In the first group, the IOL were placed in the capsular bag after lens extraction. In the second group, rabbits received TWP therapy after IOL implantation. And in the third group, rabbit received prednisone therapy after IOL implantation. Aqueous humor samples were aspirated on the 1st, 3rd, 7th, and 14th postoperative day. A modified double antibodies indirect sandwich EL ISA was used to detect for the presence of TNF. The data were closely studied by means of analysis of variance with SAS software.Results; It was found that TNF level in aqueous humor reached its maximum on the 7th postoperative day in the group with IOL implantation. It was also found that the TNF levels in aqueous humor on the 7th and 14th postoperative day were

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

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.

Evaluation of leptin,interleukin-1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

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.

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.

Studies on structural features of human tumor necrosis factor

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TUMOR NECROSIS FACTOR－α ALTERS PROTEINMETABOLISM AND CELL－CYCLE KINETICSIN MALIGNANT TUMOR

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.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

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.

EFFECTS OF PHYTOLACCA ACINOSA POLYSACCHARIDES I ON CYTOTOXICITY OF MACROPHAGES AND ITS PRODUCTION OF TUMOR NECROSIS FACTOR AND INTERLEUKIN 1

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.

Roles of tumor necrosis factor alpha on sperm acrosin activity and acrosome reaction

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.