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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2312.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Pioglitazone Inhibits the Expression of Inflammatory Cytokines From Both Monocytes and Lymphocytes in Patients With Impaired Glucose Tolerance

Wei-Yang Zhang; Eric A. Schwartz; Paska A. Permana; Peter D. Reaven

From the Department of Medicine, Section of Endocrinology, Phoenix Veteran’s Affairs Health Care System, Ariz.

Correspondence to Peter Reaven, Department of Medicine, Section of Endocrinology, Phoenix Veteran’s Affairs Health Care System, 650 E. Indian School Road, Phoenix, AZ 85012-1892. E-mail peter.reaven{at}va.gov

Objective— The current study determines whether pioglitazone (PIO) therapy reduces both monocyte and lymphocyte inflammatory activity and their ability to induce inflammation in other tissues.

Methods and Results— Monocyte and lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first shown to be greater in subjects with impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance. Sixty-six IGT subjects were then randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects had lower triglycerides and higher HDL cholesterol (P<0.05) than did subjects receiving placebo. Monocyte gene and protein expression of IL-1β, IL-6, and IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO therapy in the resting state, as well as after lipopolysaccharide (LPS) stimulation (P<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression were decreased by nearly 50% in human adipocytes exposed to conditioned media from monocytes or lymphocytes from PIO treated subjects.

Conclusion— These results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and protein expression from both monocytes and lymphocytes. This intervention also reduces the inflammatory cross-talk between these immune cells and adipose tissue, which could in turn contribute to the metabolic improvements resulting from PIO therapy.

Key Words: thiazolidinediones • cytokine • monocytes • lymphocytes • adipose tissue

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