More MS news articles for Feb 2002

Peroxisome Proliferator-Activated Receptor-[gamma] Agonist 15-Deoxy-[Delta](12,14)(12,14)-Prostaglandin J(2) Ameliorates Experimental Autoimmune Encephalomyelitis

J Immunol 2002 Mar 1;168(5):2508-2515
Diab A, Deng C, Smith JD, Hussain RZ, Phanavanh B, Lovett-Racke AE, Drew PD, Racke MK.
Department of Neurology and Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390. Department of Anatomy and Neurobiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.

Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear hormone receptor superfamily that includes receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response.

Previous studies dealing with PPAR-[gamma] expression in the immune system have been limited.

Recently, PPAR-[gamma] was identified in monocyte/macrophage cells.

In this study we examined the role of PPAR-[gamma] in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis.

The hypothesis we are testing is whether PPAR-[gamma] plays an important role in EAE pathogenesis and whether PPAR-[gamma] ligands can inhibit the clinical expression of EAE.

Initial studies have shown that the presence of the PPAR-[gamma] ligand 15-deoxy-[Delta](12,14)-PGJ(2) (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac(1--11) TCR-transgenic mice.

15d-PGJ2 suppressed IFN-[gamma], IL-10, and IL-4 production by both Con A- and myelin basic protein Ac(1--11) peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay.

Culture of encephalitogenic T cells with 15d-PGJ2 in the presence of Ag reduced the ability of these cells to adoptively transfer EAE.

Examination of the target organ, the CNS, during the course of EAE revealed expression of PPAR-[gamma] in the spinal cord inflammatory infiltrate.

Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease.

These results suggest that PPAR-[gamma] ligands may be a novel therapeutic agent for diseases such as multiple sclerosis.