Interleukin-8 production in human adipose tissue. Inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin

Obesity and Type 2 diabetes are associated with an increased risk of develo ping cardiovascular disease. Reports have suggested that the chemokine, int erleukin-8, may be involved in the development of diabetic macroangiopathy as well as in the pathogenesis of atherosclerosis. Two classes of drugs, th e biguanides and the insulin-sensitizing thiazolidinediones seem to have ad ditional beneficial effects on cardiovascular risk-factors besides their ef fects on glucose homeostasis, In this study, we investigated the effects of the thiazolidinedione, Ciglitazone, the peroxisome proliferator-activated receptor alpha-agonist 5,8,11,14-eicosatetraynoic acid (ETYA) and the bigua nide, Metformin on interleukin-8 gene expression and production in human ad ipose tissue in vitro. Ciglitazone 10-100 M inhibited interleukin-8 release by 25-33% (p < 0.05) and mRNA expression by 33-60% (p < 0.05). Metformin 0 .1-10 mM inhibited interleukin-1 release by 20 - 50 % (p < 0.05) and mRNA e xpression by 20 - 90 % (p < 0.05). However, ETYA did not effect the product ion of interleukin-8 in the adipose tissue. In conclusion, we demonstrate t he ability of two anti-diabetic compounds to decrease the release of interl eukin-8 from human adipose tissue in vitro. These findings open the possibi lity that the beneficial effects on cardiovascular risk-factors of these an ti-diabetic compounds might involve a reduction in the interleukin-8 produc ed in human adipose tissue.