Glatiramer acetate (Copaxone) regulates nitric oxide and related cytokine secretion in experimental autoimmune encephalomyelitis.
Nitric oxide (NO) is an important mediator involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). We examined the effect of glatiramer acetate (GA), an agent with suppressing effect on EAE and of therapeutic value for the treatment of MS, on the secretion of NO, as well as of the NO regulating cytokines. We observed that induction of EAE leads to 4-fold elevation in NO secretion and that treatment of the EAE mice by GA indeed leads to a significant reduction in the NO secretion by the splenocytes in response to the encephalitogen. A parallel decrease was observed in the secretion of the NO inducing cytokine IL-1beta. On the other hand, the secretion level of NO modulating cytokines IL-10 and IL-13 was significantly augmented. The correlation between these findings and the therapeutic effect of GA is discussed.
Kayhan
Basak
B
Department of Immunology, The Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel.
Aharoni
Rina
R
Arnon
Ruth
R
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D000068717:Glatiramer Acetate; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D018793:Interleukin-13; D008070:Lipopolysaccharides; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D000068717:Glatiramer Acetate