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

Diabetes Res Clin Pract. 1999 Mar;43(3):147-54. doi: 10.1016/s0168-8227(99)00005-4.


It has recently been indicated that tumor necrosis factor-alpha (TNF-alpha) production is increased under chronic hyperglycemia and TNF-alpha has harmful effects on insulin sensitivity and possibly on chronic diabetic complications. Therefore it will be favorable for diabetes treatment if anti-diabetic agents also have anti-TNF-alpha activities. In this study, we have investigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamide) and a thiazolidinedione (troglitazone) on lipopolysaccharide-induced TNF-alpha production, which was evaluated by immunoassay and bioassay, in vivo using mice and partly in vitro using human peripheral blood mononuclear cells. Gliclazide significantly inhibited TNF-alpha production in vivo and also 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, troglitazone inhibited action rather than production of TNF-alpha in vivo. In vitro troglitazone (10(-4) mol/l) significantly reduced cytolytic activity of TNF-alpha against LM cells. These results indicate that gliclazide and troglitazone have inhibitory effect on TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Cells, Cultured
  • Chromans / pharmacology*
  • Chromans / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gliclazide / pharmacology*
  • Gliclazide / therapeutic use
  • Glyburide / pharmacology*
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Interleukin-1 / blood
  • Interleukin-6 / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use
  • Thiazolidinediones*
  • Troglitazone
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Chromans
  • Hypoglycemic Agents
  • Interleukin-1
  • Interleukin-6
  • Thiazoles
  • Thiazolidinediones
  • Tumor Necrosis Factor-alpha
  • Gliclazide
  • Troglitazone
  • Glyburide