The immunotoxicologic effects of drugs on host defense have been studied widely using various animal models of infection. Here we describe a new approach to testing host defense by using a single organism ( Candida albicans ) in CBA/J mice. The model is configured to test 3 effector systems via different routes of inoculation to stimulate different effector arms of the immune response.Nonspecific immunity was evaluated by C. albicans colony-forming unit (CFU) count from the spleen at 2 hr (uptake) and ≥22 hr (clearance) following intravenous inoculation. Cell-mediated immunity was assessed by CFU count from an intramuscular injection site 6 days postinoculation. Humoral immunity was assessed by anti-Candida antibody titer, following multiple subcutaneous immunizations with C. albicans. Finally, overall immunity was evaluated following intravenous injection using survival as the endpoint. Histopathological, immunohistochemical, and electron microscopic evaluation of selected tissues revealed the involvement of the expected cell types in the different effector systems. Several immunomodulatory drugs—dexamethasone, cyclosporine, liposomal muramyltripeptide phosphatidylethanolamine, and SK&F 105685—were evaluated in the C. albicans model. Dexamethasone impaired host defense against C. albicans by suppressing all endpoints measured. Similarly, cyclosporine showed broad immunosuppressive activity, with the exception of yeast uptake from the spleen. In contrast, muramyl tripeptide-phosphatidylethanolamine enhanced all but cell-mediated immunity to C. albicans. SK&F 105685 displayed both stimulatory and inhibitory effects on immune responses to the infection. Our studies demonstrate that a single organism-based approach can be a useful method for evaluating the immunological hazards of drugs on host resistance to infection.

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The relationships between antibodies against human soluble complement receptor 1 (hsCR1) were studied in rodents, dogs, nonhuman primates, and humans. An antibody response occurred in all species except humans. The anti-hsCR1 antibodies from the various species were characterized to determine if they recognize similar epitopes on the hsCR1 molecule. Dog and monkey sera, positve for hsCR1 binding, were used as blocking antibodies against mouse anti-hsCR1 monoclonal antibodies as well as mouse and rat anti-hsCR1-positive sera. Human sera (blood group antisera: anti-Knops, anti-McCoy, anti-Knops/McCoy, anti-Swain-Langley) and serum from one burn patient (who became seropositive despite ever receiving treatment with hsCR1) were also used to test blocking of mouse, rat, dog, and monkey anti-hsCR1. Characterization of anti-hsCR1 antibodies from different species demonstrated that hsCR1 causes divergent antibody responses among animals. While mouse, rat, and dog antibodies cross inhibit binding by approximately 50%, monkey antibodies recognize primarily different epitopes of the hsCR1 molecule. Moreover, human antibodies binding hsCR1 are completely different from the animal antibodies, including monkey. This study indicates that although hsCR1 is immunogenic in animals, there is a difference in response between species, particularly between nonprimates and primates, and finally, that this antibody response is not predictive for humans.

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