Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFkappaB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

ABSTRACT: Background Rosiglitazone not only improves insulin-sensitivity, but also exerts anti-inflammatory effects. We have now examined in type 2 diabetic patients if these effects are reflected by changes in mRNA expression in peripheral blood mononuclear cells (PBMCs) to see if these cells can be used to study these anti-inflammatory effects at the molecular level in vivo. Method Eleven obese type 2 diabetic patients received rosiglitazone (2x4 mg/d) for 8 weeks. Fasting blood samples were obtained before and after treatment. Ten obese control subjects served as reference group. The expression of NFkappaB-related genes and PPARgamma target genes in PBMCs, plasma TNFalpha, IL6, MCP1 and hsCRP concentrations were measured. In addition, blood samples were obtained after a hyperinsulinemic-euglycemic clamp. Results Rosiglitazone reduced plasma MCP1 and hsCRP concentrations in diabetic patients (-9.5 +/- 5.3 pg/mL, p=0.043 and -1.1 +/- 0.3 mg/L p=0.003), respectively). For hsCRP, the concentration became comparable with the non-diabetic reference group. However, of the 84 NFkappaB-related genes that were measured in PBMCs from type 2 diabetic subjects, only RELA, SLC20A1, INFgamma and IL1R1 changed significantly (p