Effects of cyclosporin A treatment on clinical course and inflammatory cell apoptosis in experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats b y inoculation with myelin basic protein (MBP) and adjuvants. Rats were trea ted with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease fol lowed by clinical recovery. Rats treated with CsA 16 or 32 mg/kg had minima l signs of EAE at the usual time after inoculation, but developed signs of disease after treatment was ceased. Rats treated with CsA 8 mg/kg had a del ayed first episode of disease and then developed a relapsing or a chronic p ersistent course of disease. CsA 4 mg/kg delayed the onset of disease. To s tudy the effects of CsA on the inflammatory infiltrate, cells were extracte d from the spinal cords of mts with EAE, 16 h after a single injection of C sA or saline. Extracted cells were labelled with antibodies to T cells, CD1 1b/c (macrophages/microglia), CD95 (Fas) and Fas ligand. CsA 4 mg/kg did no t alter the composition of the inflammatory infiltrate. Treatment with high er single doses of CsA caused a dose-dependent decline in the percentage of T cell receptor (TCR) alpha beta(+) cells in the inflammatory infiltrate. All doses of CsA caused a significant increase in the number and percentage of cells that were apoptotic. CsA treatment caused an increase in the perc entages of CD5(+) and TCR alpha beta(+) cells that were apoptotic. There wa s a decline in the percentage of apoptotic T cells that were V beta 8.2(+), compared to the percentage of non-apoptotic T cells that were V beta 8.2(), in CsA treated rats compared to saline-treated controls. This suggests t hat, while CsA treatment caused a non-specific increase in the overall leve l of T cell apoptosis in the spinal cord, it abrogated the selective apopto sis of V beta 8.2(+) encephalitogenic T cells that normally occurs during s pontaneous recovery from acute EAE. (C) 1999 Elsevier Science B.V. All righ ts reserved.