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
Pa. Mccombe et al., 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, J NEUROIMM, 97(1-2), 1999, pp. 60-69
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.