Pioglitazone inhibits the expression of inflammatory cytokines from both monocytes and lymphocytes in patients with impaired glucose tolerance.

Abstract

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-1 beta, 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.

CONCLUSIONS:

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.

• Authors: Wei-Yang Zhang, Eric A Schwartz, Paska A Permana, Peter D Reaven
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 28 Issue 12 Pg. 2312-8 (Dec 2008) ISSN: 1524-4636 [Electronic] United States
• PMID: 18818415 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cholesterol, HDL
• Culture Media, Conditioned
• Cytokines
• Hypoglycemic Agents
• Inflammation Mediators
• Thiazolidinediones
• Triglycerides
• Pioglitazone

Topics

• Adipocytes (drug effects, metabolism)
• Adult
• Aged
• Cell Line
• Cholesterol, HDL (blood)
• Culture Media, Conditioned
• Cytokines (blood, genetics)
• Down-Regulation (drug effects)
• Female
• Glucose Intolerance (blood, drug therapy, genetics, immunology)
• Humans
• Hypoglycemic Agents (pharmacology)
• Inflammation Mediators (blood)
• Lymphocytes (drug effects, immunology, metabolism)
• Male
• Middle Aged
• Monocytes (drug effects, immunology, metabolism)
• Pioglitazone
• Thiazolidinediones (pharmacology)
• Triglycerides (blood)
• Young Adult