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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.

Abstract：

:Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by inoculation with myelin basic protein (MBP) and adjuvants. Rats were treated with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease followed by clinical recovery. Rats treated with CsA 16 or 32 mg/kg had minimal 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 delayed first episode of disease and then developed a relapsing or a chronic persistent course of disease. CsA 4 mg/kg delayed the onset of disease. To study the effects of CsA on the inflammatory infiltrate, cells were extracted from the spinal cords of rats with EAE, 16 h after a single injection of CsA or saline. Extracted cells were labelled with antibodies to T cells, CD11b/c (macrophages/microglia), CD95 (Fas) and Fas ligand. CsA 4 mg/kg did not alter the composition of the inflammatory infiltrate. Treatment with higher single doses of CsA caused a dose-dependent decline in the percentage of T cell receptor (TCR) alphabeta+ 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 percentages of CD5+ and TCR alphabeta+ cells that were apoptotic. There was a decline in the percentage of apoptotic T cells that were Vbeta8.2+, compared to the percentage of non-apoptotic T cells that were Vbeta8.2+, in CsA treated rats compared to saline-treated controls. This suggests that, while CsA treatment caused a non-specific increase in the overall level of T cell apoptosis in the spinal cord, it abrogated the selective apoptosis of Vbeta8.2+ encephalitogenic T cells that normally occurs during spontaneous recovery from acute EAE.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

McCombe PA,Harness J,Pender MP

doi

10.1016/s0165-5728(99)00047-8

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

60-9

issue

1-2

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(99)00047-8

journal_volume

pub_type

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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.