Introduction: Lichen planus is a skin and mucosal disease with an unknown etiology. However, a number of factors are known to play a role. One of these factors is inflammatory cytokines, such as TNF-α, which play a key role in inflammation. The aim of this study was to evaluate serum levels of TNF-a in patients with oral lichen planus (OLP) and (contact/drug-induced) oral lichenoid reactions (OLR) in comparison with normal controls.Materials and methods: In this descriptive-analytical, cross-sectional study, 10 OLP (mean age 46.84±8.59), 20 OLR patients (mean age 49.18±13.34) and 20 normal controls (mean age 39.86±6.99) were compared and the serum levels of TNF-a were measured by ELISA. Data were analyzed with SPSS 16, using Kruskal-Wallis test (a=0.05).Results: The OLR patients, OLP patients and normal group exhibited no significant differences in the serum levels of TNF-a (p value=0.465). The mean serum levels of TNF-a in OLR and OLP patients and in healthy individuals were 10.45, 30.76 and 50.73, respectively.Conclusion: Under the limitations of the present study, there were no significant differences in the serum levels of TNF-α in patient with OLP and OLR and healthy subjects. Therefore, TNF-a cannot be used to make a distinction between lichen planus and lichenoid reaction lesions.

Background: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is a correlation between up-regulation of a variety of cytokines with inflammatory reactions in multiple sclerosis lesions. This study aimed to investigate the effects of high-intensity resistance exercise program on prevention of experimental autoimmune encephalomyelitis (EAE) (a model for studying multiple sclerosis).Methods: Resistance exercises were performed for 6 weeks, 5 days a week. Training program started with 50% of rats' body weight. In the first session, animals performed 8 to 10 repetitions (up the ladder) with 2-minute rest intervals. Rats were immunized with spinal cord and complete adjuvant of guinea pigs. Disease process and changes in rats' weights were measured every day. Experimental autoimmune encephalomyelitis model was induced at the end of the sixth week of training.Findings: Resistance training in Lewis female rats with experimental autoimmune encephalomyelitis resulted in a significant reduction in tumor necrosis factor-alpha (TNF-a) (P=0.001) and a significant increase in interleukin-10 (IL-10) (P=0.001). However, it did not cause significant changes in Brain-Derived Neurotrophic Factor (BDNF) (P=0.055). In addition, clinical symptoms in exercised rats were postponed.Conclusion: Regarding the results, it appears that resistance exercises with necessary duration and intensity delay the onset, reduce the severity of clinical symptoms, and decrease TNF-a, increase IL-10, with no change in BDNF, in Lewis rats with experimental autoimmune encephalomyelitis.

Background: Preeclampsia is the most common serious disorder during pregnancy and studies show several immune-related processes in its pathophysiology. The role of cytokines and their expression remains controversial in this field. One of the cytokines of interest in recent studies has been TNF-a, which has been shown to have a higher level in maternal plasma of preeclamptic women.Objectives: This study was designed to evaluate the role of TNF-a polymorphism at position -238 in the risk of developing preeclampsia during pregnancy.Patients and Methods: One hundred fifty three preeclamptic cases and 140 healthy pregnant women were retrieved from two major hospitals of Mashhad, Iran. Methods a case-control study were designed. Anyone with a history of inflammatory disease, hypertension, or chronic kidney disease was excluded. DNA was extracted from peripheral blood leukocytes. Both groups were genotyped for the polymorphism of the TNF-a gene at position -238 by the RFLP method with Ava II enzyme. Allele and genotype frequencies were compared using one-way ANOVA and the Fisher's exact test.Results: There were significant differences between the two groups in TNF-a genotype at position -238 (P<0.001). In the preeclamptic group, the frequency of the AA genotype was higher (P<0.001) and the frequency of the GG genotype was lower (P<0.001). The overall prevalence of the A allele at position -238 was higher in preeclamptic cases (P<0.001).Conclusion: In this study group, TNF-a -238 polymorphism was shown to be different in preeclamptic and non-preeclamptic pregnant women. The AA genotype and the A allele may carry an increased risk for developing of preeclampsia.

Tumor necrosis factor-alpha (TNF-a) is a pro-inflammatory cytokine produced by a variety of cells, including hematopoietic and non-hematopoietic cells, malignant cells, macrophages, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, astrocytes, endothelial cells, and smooth muscle cells. TNF-a is a homo-trimeric molecular whose individual subunits are composed of antiparallel beta-sheets, forming a regular triangular prism shape. TNF-α binds to three receptor molecules through its receptor-binding sites, which are at the base of its pyramid structure. Biological responses to TNF-a are mediated through two different receptors: TNFR1 and TNFR2.These receptors are trans membrane glycoproteins with extracellular domains containing multiple cysteine-rich repeats that are structurally and functionally homologous, and the intracellular domains that are discrete and transduce their signals through both overlapping and distinct pathways. However, though TNF-a was initially discovered as an anti-tumor agent, it has been revealed that TNF-α and other ligands of this family are involved in some diseases like cancer, neurological, pulmonary, cardiovascular and autoimmune diseases and metabolic disorders. In general, TNF-aactivates the control systems involved in cell proliferation, differentiation, inflammation and cell death, and the regulation of immune system. Although a normal level of TNF-a is very important for the regulation of immune responses, the persistence of the immune response as a result of inappropriate and excessive production of TNF-α can cause some inflammatory or autoimmune diseases. Accordingly, either neutralization TNF-a or blockade of its receptors using TNF-a inhibitors can be an effective therapeutic strategy to prevent or treat such inflammatory diseases. Several methods have been used to inhibit TNF-a, including the production of chimeric or fully human antibodies, soluble TNF-a receptors, or anti-TNF-a small molecules. The two previous agents are mostly capable of inhibiting the binding of TNF-a to its associated receptors, while anti-TNF-a small molecules, in addition to the above, inhibit the biosynthesis of TNF-a by blocking TNF-a mRNA biosynthesis, through the inhibition of its post-translational processing, or by blocking TNF-a receptors. Therefore, in this review article, we discuss the structure and characteristics of TNF-a and its related receptors: TNF-a signaling, TNF-a-mediated inflammatory diseases as well as TNF-a inhibition strategies.

Background: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-a), is a pathogenic element for a number of disorders. Previous studies have reported that the -1031 T/C and -238 G/A polymorphisms in the promoter region of the TNF-a gene are important factors in reproductive-related disorders. One of the most common gynecological diseases of women during the reproductive years is endometriosis. This study aims to assess an association between the -1031 T/C, -238 G/A and -308 G/A polymorphisms of the TNF-a gene promoter region to endometriosis.Materials and Methods: In this case-control study, we enrolled 65 endometriosis patients and 65 matched healthy control women by simple sampling. Polymerase chain reaction (PCR) analysis was used to analyze -1031 T/C, -238 G/A and -308 G/A polymorphisms in the TNF-a gene promoter region. Statistical analysis was performed using the chi-square test. P values less than 0.05 were considered statistically significant. Results: We found a strong association between the -1031 T/C polymorphism in the promoter region of the TNF-a gene with endometriosis (P=0.001). There were no significant associations between the -238 G/A (P=0.243) and -308 G/A (P=1) polymorphisms with endometriosis and again endometriosis stages have no association with these polymorphisms. Conclusion: The -1031 T/C polymorphism and CC genotype can be used as a relevant marker to identify women at risk of developing endometriosis.

Background and purpose: Several laboratories have developed culture systems including maturation factors for human DC from peripheral blood monocytes. We comprehensively studied the effect of addition of poly (I-C) to standard maturation stimulus, MCM and TNF-a on maturation of monocyte derived DCs and their ability to elicit T cell responses.Materials and methods: A short (4-day) priming of plastic adherent monocytes with granulocytemacrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) followed by allogenic tumor antigen pulsing and addition of MCM and TNF-a with or without poly (I-C) to generate fully mature and stable DCs. Phenotypic and functional analysis were carried out using anti CD14, HLA-DR and CD83 monoclonal antibodies, mixed lymphocyte reaction (MLR), phagocytic activity and cytokine release by DC stimulated T lymphocytes.Results: We found that fully matured DCs with large amount cytoplasm and copious dendritic projections were visible at the end of culturing period in the presence of MCM and TNF-a with or without rpoly (I-C). Flow cytometric analysis using anti-CD14, HLA-DR and CD83 revealed that addition of poly (I-C) to conventional maturation factors results in decreased expression of CD14 and increased expression of HLA-DR and CD83. Functionally, MCM and TNF-a with poly (I-C) treated DCs showed a little stronger mixed leukocyte reaction Analysis of phagocytic activity showed that addition of poly (I-C) reduced FITC-conjugated bead uptake and increased mean fluorescent intensity (MFI) of phagocytic DCs. Furthermore our results revealed that additional treatment of DCs with poly (I-C) results in reduction of IL-12: IL-10 and IFN-γ: IL-4 ratios in DC and DC-primed T cell supernatants respectively.Conclusion: Our results support this idea that use of the MCM, TNF-a and poly (I-C) as maturation factor could gnerates more mature monocyte derived DCs that prime T lymphocytes to TH2 type cytokine release.