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 andIL-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.
RCT Entities:
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: Christian Setz; Maximilian Große; Janina Auth; Maria Fröba; Pia Rauch; Alexander Bausch; Matthew Wright; Ulrich Schubert Journal: Int J Mol Sci Date: 2022-06-20 Impact factor: 6.208
Authors: Hideaki Nakaya; Barbara D Summers; Andrew C Nicholson; Antonio M Gotto; David P Hajjar; Jihong Han Journal: Am J Pathol Date: 2009-05-12 Impact factor: 4.307
Authors: Valentina Spigoni; Angela Picconi; Monia Cito; Valentina Ridolfi; Sabrina Bonomini; Chiara Casali; Ivana Zavaroni; Luigi Gnudi; Marco Metra; Alessandra Dei Cas Journal: PLoS One Date: 2012-11-05 Impact factor: 3.240