Immunomodulation of experimental autoimmune encephalomyelitis in the Lewis rats by Lovastatin.
Previous studies have demonstrated the immunomodulatory potential of Lovastatin, a hydroxy methyl glutaryl-CoA reductase inhibitor, in lessening the clinical and histological manifestations in the neuroinflammatory animal model experimental autoimmune encephalomyelitis (EAE) (Neurosci. Lett., 269 (1999) 71, and J. Neurosci. Res., 66 (2001) 155). To determine the mechanism behind the observed amelioration of EAE by Lovastatin, we examined the cytokine profile of stimulated splenocytes from control, EAE and Lovastatin treated EAE rats. Splenocytes from Lovastatin-treated EAE rats showed decreased levels of interferon-gamma, a Th1 type cytokine, while interleukin (IL)-10, a Th2 type cytokine, was markedly increased as compared to untreated EAE animals. In addition, we also observed reduced levels of IL-6 and nitric oxide production in lipopolysaccharide-stimulated splenocytes isolated from Lovastatin-treated animals. This study documents for the first time that Lovastatin induces a bias towards Th2 cytokines ex vivo, and as a result may be of therapeutic value for cell-mediated diseases such as multiple sclerosis.
Stanislaus
Romesh
R
Department of Pediatrics, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.
Gilg
Anne G
AG
Singh
Avtar K
AK
Singh
Inderjit
I
D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008148:Lovastatin / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology; D009573:Nitrites / Q000032:analysis; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D004676:Myelin Basic Protein; D009573:Nitrites; D010835:Phytohemagglutinins; D016753:Interleukin-10; D007371:Interferon-gamma; D008148:Lovastatin