title: Evidence for a potent antiinflammatory effect of rosiglitazone.
abstract: We have recently demonstrated a potent antiinflammatory effect of troglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) and a partial agonist of PPARalpha in both the nondiabetic obese and diabetic obese subjects. We have now investigated the antiinflammatory actions of rosiglitazone, a selective PPARgamma agonist. Eleven nondiabetic obese subjects and 11 obese diabetic subjects were each given 4 mg of rosiglitazone daily for a period of 6 wk. Fasting blood samples were obtained at 0, 1, 2, 4, 6, and 12 wk (6 wk after the cessation of rosiglitazone). Eight obese subjects and five obese diabetic subjects were also included in the study as control groups. Fasting blood samples were obtained from the control groups at 0, 1, 2, 4, and 6 wk only. Nuclear factor kappaB (NFkappaB)-binding activity in mononuclear cells, plasma monocyte chemoattractant protein-1 (MCP-1), TNF-alpha, soluble intercellular adhesion molecule-1, C-reactive protein (CRP), and serum amyloid A (SAA) were measured. Blood glucose concentration changed significantly at 6 wk only in the obese diabetic subjects after rosiglitazone treatment for 6 wk, whereas insulin concentration decreased significantly at 6 wk in both groups. NFkappaB-binding activity in mononuclear cell nuclear extract fell in both obese and obese diabetic subjects (P < 0.02). Rosiglitazone treatment resulted in a reduction in plasma MCP-1 and CRP in both groups (P < 0.05). Plasma TNF-alpha and SAA concentrations were inhibited significantly in the obese group (P < 0.05) but not in the obese diabetic subjects. NFkappaB-binding activity and plasma MCP-1, CRP, SAA, and TNF-alpha did not change in the obese and obese diabetic control groups. We conclude that rosiglitazone, a selective PPARgamma agonist, exerts an antiinflammatory effect at the cellular and molecular level, and in plasma. These observations may have implications for atherogenesis in the long term in subjects treated with rosiglitazone and possibly other thiazolidinediones.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, State University of New York, and Kaleida Health, Buffalo, New York 14209, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Mohanty
authors.forename: Ahmad
authors.initials: A
authors.lastname: Aljada
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Deborah
authors.initials: D
authors.lastname: Hofmeyer
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Tufail
authors.initials: T
authors.lastname: Syed
authors.forename: Waddah
authors.initials: W
authors.lastname: Al-Haddad
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhindsa
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001786:Blood Glucose; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity; D000077154:Rosiglitazone; D012995:Solubility; D045162:Thiazolidinediones / Q000008:administration & dosage*; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D020672:I-kappa B Proteins; D007328:Insulin; D016328:NF-kappa B; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein