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

• Published in: Diabetes research and clinical practice 1999-03, Vol.43 (3), p.147-154
• Main Authors: Fukuzawa, M., Satoh, J., Qiang, X., Miyaguchi, S., Sakata, Y., Nakazawa, T., Ikehata, F., Ohta, S., Toyota, T.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biological Assay; Cells, Cultured; Chromans - pharmacology; Chromans - therapeutic use; Enzyme-Linked Immunosorbent Assay; Female; Glibenclamide; Gliclazide; Gliclazide - pharmacology; Gliclazide - therapeutic use; Glyburide - pharmacology; Glyburide - therapeutic use; Hormones. Endocrine system; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin resistance; Interleukin-1 - blood; Interleukin-6 - blood; Male; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Thiazoles - pharmacology; Thiazoles - therapeutic use; Thiazolidinediones; TNF-α; Troglitazone; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(99)00005-4

It has recently been indicated that tumor necrosis factor-α (TNF-α) production is increased under chronic hyperglycemia and TNF-α 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-α activities. In this study, we have investigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamide) and a thiazolidinedione (troglitazone) on lipopolysaccharide-induced TNF-α 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-α production in vivo and also in vitro at a concentration of 10 −3 mol/l. However, glibenclamide had neither effect on TNF-α production nor action. On the other hand, troglitazone inhibited action rather than production of TNF-α in vivo. In vitro troglitazone (10 −4 mol/l) significantly reduced cytolytic activity of TNF-α against LM cells. These results indicate that gliclazide and troglitazone have inhibitory effect on TNF-α.