Peroxisome Proliferator-Activated Receptor α Agonists as Therapy for Autoimmune Disease

Amy E. Lovett-Racke, Rehana Z. Hussain, Sara Northrop, Judy Choy, Anne Rocchini, Lela Matthes, Janet A. Chavis, Asim Diab, Paul D. Drew, Michael K. Racke

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ ligands, which include the naturally occurring PG metabolite 15-deoxy-Δ12,14-PGJ 2 (15d-PGJ2), as well as thiazolidinediones, have been shown to have anti-inflammatory activity. The PPARα agonists, gemfibrozil, ciprofibrate, and fenofibrate, have an excellent track history as oral agents used to treat hypertriglyceridemia. In the present study, we demonstrate that these PPARα agonists can increase the production of the Th2 cytokine, IL-4, and suppress proliferation by TCR transgenic T cells specific for the myelin basic protein Ac1-11, as well as reduce NO production by microglia. Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis. More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-γ and promoting IL-4 secretion. These results suggest that PPARα agonists such as gemfibrozil and fenofibrate, may be attractive candidates for use in human inflammatory conditions such as multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)5790-5798
Number of pages9
JournalJournal of Immunology
Volume172
Issue number9
DOIs
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lovett-Racke, A. E., Hussain, R. Z., Northrop, S., Choy, J., Rocchini, A., Matthes, L., Chavis, J. A., Diab, A., Drew, P. D., & Racke, M. K. (2004). Peroxisome Proliferator-Activated Receptor α Agonists as Therapy for Autoimmune Disease. Journal of Immunology, 172(9), 5790-5798. https://doi.org/10.4049/jimmunol.172.9.5790