Rosiglitazone Reduces Inflammatory Response and Tissue Damage in...

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Rosiglitazone Reduces Inflammatory Response and Tissue Damage in Arthritis

Model

NEW YORK (Reuters Health) Jan 22 - Rosiglitazone, a peroxisome

proliferator-activated receptor (PPAR)-gamma receptor ligand, reduces the

evolution of type II collagen-induced arthritis in mice, according to a

report in the December 2003 issue of Arthritis & Rheumatism.

Recent studies suggest that PPAR-gamma may participate in the control of

inflammation by modulating the production of inflammatory mediators, the

authors explain. Rosiglitazone, used principally in treating type 2

diabetes, might ameliorate the development of arthritis by interfering with

the PPAR-gamma-mediated inflammatory response.

To test this hypothesis, Dr. Salvatore Cuzzocrea from University of Messina,

Italy and colleagues studied the effects of rosiglitazone treatment on the

development of arthritis caused by injection of type II collagen into mice.

Treatment with rosiglitazone significantly reduced joint inflammation, the

authors report, resulting in both a lower incidence and lesser severity of

arthritis.

Rosiglitazone treatment was associated with significant reductions in

collagen immunization-induced weight loss and hind paw swelling, the report

indicates. Rosiglitazone-treated mice also had significantly reduced bone

erosion and necrosis in the joints.

Activity levels of the chemokines MIP-1alpha and MIP-2 and the granulocyte

lysosome-specific enzyme myeloperoxidase were markedly reduced in

rosiglitazone-treated mice (compared with vehicle-treated mice), the

researchers note.

Moreover, rosiglitazone treatment significantly reduced the production of

such putative inflammatory mediators as TNF-alpha, IL-1beta, IL-6, iNOS, and

COX-2, the investigators report.

Dr. Cuzzocrea told Reuters Health that, based on these data, PPAR-gamma

ligands may represent a new class of drugs for treating chronic arthritis.

" We have recently tested an endogenous PPAR-gamma ligand in a model of

colitis and observed a protective effect, " Dr. Cuzzocrea said. Based on this

and on preliminary data with rosiglitazone, it appears that these agonists

will have beneficial effects in other experimental models of chronic

inflammation, he added.

Arthritis Rheum 2003;48:3544-3556