Inhibition of tumor necrosis factor-alpha with anti-diabetic agents

It has recently been indicated that tumor necrosis factor-alpha (TNF-alpha) production is increased under chronic hyperglycemia and TNF-alpha has harm ful effects on insulin sensitivity and possibly on chronic diabetic complic ations. Therefore it will be favorable for diabetes treatment if anti-diabe tic agents also have anti-TNF-alpha activities. In this study, we have inve stigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamid e) and a thiazolidine-dione (troglitazone) on lipopolysaccharide-induced TN F-alpha production, which was evaluated by immunoassay and bioassay, in viv o using mice and partly in vitro using human peripheral blood mononuclear c ells. Gliclazide significantly inhibited TNF-alpha production in vivo and a lso in vitro at a concentration of 10(-3) mol/l. However, glibenclamide had neither effect on TNF-alpha production nor action. On the other hand, trog litazone inhibited action rather than production of TNF-alpha in vivo. In v itro troglitazone (10(-4) mol/l) significantly reduced cytolytic activity o f TNF-alpha against LM cells. These results indicate that gliclazide and tr oglitazone have inhibitory effect on TNF-alpha. (C) 1999 Elsevier Science I reland Ltd. All rights reserved.