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 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.
Fukuzawa
M
M
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Satoh
J
J
Qiang
X
X
Miyaguchi
S
S
Sakata
Y
Y
Nakazawa
T
T
Ikehata
F
F
Ohta
S
S
Toyota
T
T
D000818:Animals; D001681:Biological Assay; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005907:Gliclazide / Q000494:pharmacology* / Q000627:therapeutic use; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D000077288:Troglitazone; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D002839:Chromans; D007004:Hypoglycemic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D013844:Thiazoles; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D005907:Gliclazide; D000077288:Troglitazone; D005905:Glyburide