The action of cyclosporin A on helminth parasites
The influence of the immunomodulatory/antiparasitic drug cyclosporin A (CsA) on parasitic infections is discussed and its effects on three helminths examined. The biology of the tapeworm Hymenolepis microstoma is reviewed and the action of CsA on this parasite investigated. Therapeutic CsA treatment was antagonistic to both juvenile and adult H.microstoma, reducing worm weight, delaying migration into the bile duct, suppressing egg production and lowering parasite survival. CsA also showed significant chemoprophylactic properties against H.microstoma CsA treatment in vivo caused gross and ultrastructural changes to the work surface and appeared to alter the permeability of the worm tegument to 14[C]-glucose in vitro. The protein composition of whole-worm and tegumentary fractions was analysed by one- and two-dimensional SDS-PAGE but was largely unaffected by drug treatment. A speculative scheme for the mode of action of CsA against H.microstoma is proposed which postulates that the work surface may be the site of action of the drug but the exact molecular target of CsA remains elusive. In marked contrast to its effect on H.microstoma, CsA delayed the normal host-mediated expulsion of H.diminuta from CBA, MF1 and BALB/C mice, enabling the parasite to reach patency. Worm recovery and weight both increased with CsA treatment. These paradoxical drug effects reflect the putative antagonism between immunosuppression and anthelmintic activity of CsA. The ability of CsA to suppress the host-mediated expulsion of H.diminuta from mice may implicate the importance of T-cells in protective immunity to this parasite. The influence of CsA treatment on the protein profiles of Schistomsoma mansoni was examined by SDS-PAGE. CsA significantly altered the concentration of a 31 kD protein sub-unit in female schistosomes and this is considered to corroborate the hypothesis that CsA targets haemoglobinase in female adult S.mansoni.