Association of two polymorphisms of tumor necrosis factor gene with acute biliary pancreatitis

AIM: To investigate TNF-α-308 and TNFB polymorphisms in acute biliary pancreatitis (ABP) and to related them to the plasma TNF-α levels.METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients (n=127) and healthy controls (n=-102)using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Reading the size of digested bands from polyacrylamide gel demonstrated the two alleles TNF1 and TNF2, or the two alleles TNFB1and TNFB2.RESULTS: The frequencies of TNF2 polymorphism and TNFB2 polymorphism were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. Patients with septic shock showed a significantly higher prevalence of the TNF2 than those without. No significant differences were found in the genotype distribution of TNF-α-308 and TNFB among different groups. Plasma TNF-α levels did not differ significantly in ASBP patients displaying different alleles of the TNF gene studied.CONCLUSION: Results indicate that TNF gene polymorphisms studied play no part in determination of disease severity or susceptibility to acute biliary pancreatitis; however, TNF2polymorphism is associated with septic shock from ASBP.Genetic factors are not important in determining plasma TNF-α levels in ASBP.

Role of NF-κB and cytokine in experimental cancer cachexia

AIM: To assess the putative involvement of NF-κB and proinflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND)on cachexia.METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing murine were inoculated subcutaneously to induce cachexia.Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNFα and IL-6 and activity of NF-κB in the spleen were investigated in all animals.RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P＜0.01), and the weight of gastrocnemius was decreased by 28.7 % (P＜0.01). No difference was found between groups in food intake (P＞0.05).Gastrocnemius weight was increased markedly (P＜0.01)body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-αand IL-6 (P＜0.01). The concentration of TNF-α (P＜0.05)and IL-6 (P＜0.01) in tumor-bearing mice was reduced after of IL-6 was slightly elevated following treatment of IND 2.0tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (ENSA). NF-κB activity a higher NF-κB activity was observed in mice treated with CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-αand IL-6 in tumor-bearing animals, which is controlled by NF-κB. Low dose of indomethacin alleviates the cachexia,decreases the activation of NF-κB and the serum levels of TNF-α and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.