Anti-schistosomal activity of cyclosporin A: studies on murine spleen cells and the influence of a cyclosporin antagonist on resistance to infection.
Mice were treated with 5-day courses of cyclosporin A (CsA) around the time of infection with Schistosoma mansoni. Recovery of lung-stage worms 4-8 days post-infection (p.i.) was substantially reduced (80%) and no sexually mature adults were recovered from the hepatic portal system at 7 weeks p.i. Flow cytometric analysis of spleen cells from CsA-treated animals during the period of maximal parasite attrition revealed transient reductions in CD3+ and CD4+ cells and in the CD4+: CD8+ ratio compared with drug vehicle-treated, infected controls. No significant numerical changes in B cells, macrophages or eosinophils were detected relative to vehicle-treated infected mice. Transfer of spleen cells from CsA-treated donors 8 days after infection failed to confer increased resistance to S. mansoni infection on untreated recipients. Moreover, concomitant administration of CsA and an inducer of interleukin-2 production (ADA-202-718) did not interfere with the anti-schistosomal effect of CsA. Despite our incomplete understanding of the in vivo properties of CsA and reports of its paradoxical effects on immune responses, these new data indicate that the influence of CsA in schistosomiasis is unlikely to be mediated by modulation of host cell mediated immunity. This contrasts with certain other anti-parasitic effects of CsA which appear to be mediated by an action on T cells.
Brannan
L R
LR
Department of Zoology, University of Aberdeen, U.K.
Chappell
L H
LH
Woo
J
J
Thomson
A W
AW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003524:Cyclosporins / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D004220:Disulfides / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects; D008297:Male; D051379:Mice; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D003524:Cyclosporins; D004220:Disulfides; C045470:ethylene-2,2'-bis(dithio)bis(ethanol)