Interleukin 12 and interleukin 10 are affected differentially by treatment of multiple sclerosis with glatiramer acetate (Copaxone).
Proinflammatory cytokines produced by Th-1 cells and cytokines with immunosuppressive properties play an important role in the pathogenesis of multiple sclerosis (MS). Glatiramer acetate (GA) is one of the most important immunomodulatory agents used in the therapy of MS. The mechanism of action of GA in MS is not yet fully explained. In our previous study we found the significant down-regulation of interleukin 18 (IL-18), a proinflammatory cytokine inducing the production of interferon gamma during therapy with GA in MS patients. The purpose of this study was to evaluate the effect of GA in a dose 20 mg daily in a period of 6 months on interleukins IL-10 and IL-12. Thirty-one patients with definite MS and 30 control subjects were the subject of our study. The interleukins levels in sera were measured by the ELISA test. A significant increase was found of IL-12 and also of IL-10 levels in MS patients in comparison with control group. We also established a significant decrease of IL-12 after 3 and 6 months of GA therapy and some insignificant differences in the level of IL-10 (the decrease after 3 months and the increase after 6 months). IL-12 is a proinflammatory cytokine secreted by blood mononuclear cells, including dendritic cells in response to antigens and mitogens and is thought to contribute to the pathogenesis of MS. Therefore the established downregulation of IL-12 as well as that previously described of IL-18 suggest a marked relationship between the clinical effect and downregulatory action of GA on proinflammatory interleukins. The insignificant change of IL-10 level observed in the course of GA therapy seems to indicate that this cytokine is not connected with the immunomodulatory effect of GA in MS.
Losy
Jacek
J
Department of Clinical Neuroimmunology, University School of Medicine and Neuroimmunological Unit, Medical Research Centre, Polish Academy of Sciences, Poznań, Poland. jlosy@mail.usoms.poznan.pl
Michałowska-Wender
Grazyna
G
Wender
Mieczysław
M
D000328:Adult; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D010455:Peptides / Q000627:therapeutic use*
D010455:Peptides; D016753:Interleukin-10; D018664:Interleukin-12; D000068717:Glatiramer Acetate