Effect of immunomodulators pyrimethamine and cimetidine on immunosuppression induced by sulfur mustard in mice.
Despite extensive world-wide research no effective therapy has been devised for the treatment and cure of patients exposed to sulfur mustard (S-M). A severe suppression of the immune system still remains the major cause of opportunist infections, septicemia and death in patients injured by S-M. In this report we present a model of S-M contamination in mice which is suitable for immunomodulation studies. Results show that differing doses of S-M caused an overall suppression of the immune response to SRBC as indicated by agglutination titers, (DTH) tests, spleen histology and spleen weight indices. In the second stage two immunomodulating agents; pyrimethamine and cimetidine were employed and their effectiveness in augmenting immune responses after S-M induced immunosuppression was evaluated. Pyrimethamine, at all doses employed, enhanced antibody titers to SRBC, augmented DTH responses, and restored splenic follicles as compared with controls only exposed to S-M. Cimetidine augmented antibody titers and enhanced DTH responses at doses of 10 and 15 mg/kg as compared with controls. At a dose of 5 mg/kg cimetidine did not exhibit any effect on titers or DTH responses. Histological studies revealed that cimetidine restored splenic follicles and increased macrophage numbers and phagocytic activity at all three doses. Spleen weight indices were not augmented by either drug. These data provide evidence that immunomodulating drugs may prove effective in countering the immunosuppressive effects of S-M.
Ebtekar
M
M
Tarbiat Modarres University, School of Medical Sciences, Immunology Department, Tehran, Iran.
Hassan
Z M
ZM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed; D007107:Immune System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009151:Mustard Gas / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011739:Pyrimethamine / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D002927:Cimetidine; D009151:Mustard Gas; D011739:Pyrimethamine