Cryptosporidiosis is a diarrheal disease in humans and other animals caused by the coccidian parasite, Cryptosporidium parvum. This study was undertaken to determine the effectiveness of dehydroepiandrosterone (DHEA) in reducing C. parvum infections in immunosuppressed adult C57BL/6N mice and to identify the immunomodulatory effects of DHEA that result in increased resistance to cryptosporidiosis. Dexamethasone-immunosuppressed mice were readily infected with C. parvum following orogastric intubation with 10(6) oocysts/mouse. DHEA treatment of these mice significantly reduced (P < 0.01) both fecal oocyst shedding and parasite colonization of the ilea. Immunosuppressed mice treated with DHEA had more splenic total T cells, CD4+ T cells, and CD8+ T cells than immunosuppressed mice that were not treated, but the differences were not always significant. Moreover, nonimmunosuppressed mice treated with DHEA had significantly more (P < 0.05) splenic total T cells, CD4+ T cells, and total B cells than nonimmunosuppressed mice that did not receive DHEA. Of particular interest was the significantly larger (P < 0.05) number of CD8+ T cells in immunosuppressed, C. parvum-infected, DHEA-treated mice compared with the same mice that were not treated. Up-regulation of the immune system by exogenous DHEA may be useful in the treatment and palliation of cryptosporidiosis.

Cryptosporidium parvum is a coccidian parasite that causes diarrheal disease in animals and humans. Severe cryptosporidial infections were noted in young adult rats immunosuppressed with the glucocorticosteroid dexamethasone (DEX). B-cell and T-cell responses to the mitogens lipopolysaccharide and concanavalin A, respectively, were depressed in the DEX-treated rats. In addition, DEX treatment suppressed serum IgG levels, in vitro IgG production, and natural killer cell activities. Previous results have shown that DEX-immunosuppressed rats treated with dehydroepiandrosterone (DHEA) exhibit significant reductions in cryptosporidiosis as determined by monitoring oocyst shedding in the feces and parasite colonization of the small intestine. Results from this study indicated that B- and T-cell responses to their respective mitogens, serum IgG levels, and in vitro IgG production were greater in DHEA-treated immunosuppressed rats than in untreated DEX-immunosuppressed rats infected with C. parvum. Similar results were demonstrated in DHEA-treated versus normal control rats infected with C. parvum. These results suggest that the effects of DHEA in reducing cryptosporidiosis are the result of a potentiation of the immune system in the immunosuppressed rats.

The aim of this study was to evaluate the efficacy of the immunomodulator dehydroepiandrosterone in the treatment of cryptosporidiosis in glucocorticoid-induced immunosuppressed rats. A significant reduction in cryptosporidial activity occurred in treated versus untreated rats as assessed by oocyst shedding intensities and examination of parasite colonization in the small intestine.

Five strains of adult mice were immunosuppressed with the synthetic glucocorticosteroid dexamethasone (DEX), administered either orally or intraperitoneally. The strains of mice used were C57BL/6N, DBA/2N, CBA, C3H/HeN, and BALB/cAnN. All mice were evaluated for susceptibility to Cryptosporidium parwum after intragastric inoculation with 106 oocysts per mouse. The DBA/2N, CBA, C3H/HeN, and BALB/cAnN mice given 0.25 ,ug of DEX per g per day orally (the dose and route previously used to infect rats with C. parvum) failed to develop chronic infections. However, the C57BL/6N mice sustained light infections during the entire 28-day experiment. The five strains of mice were also administered DEX intraperitoneally at concentrations ranging from 62.5 to 500 R,g/day. Only the C57BL/6N mice given DEX at 125 ,ug/day developed chronic infections which persisted over 10 weeks, suggesting that the genetic background of the mouse plays a role in determining susceptibility to cryptosporidiosis following immunosuppression with DEX. We believe that the C57BL/6N mouse model will prove to be superior to other animal models for evaluating potential anticryptosporidial agents, as well as for elucidating the immunological defects that allow C. parvum to establish chronic infections, because of cost effectiveness and ease in maintenance, breeding, and handling. We also evaluated the C3H/HeJ/beige mouse (lacks natural killer cell activity) and the C57BL/6N mouse maintained on a low-protein diet to induce immunosuppression. Neither of these mice exhibited heavy cryptosporidial infections.

Cryptosporidiosis, a parasitic disorder caused by Cryptosporidium parvum, is frequently a fulminating and life-threatening disease in immunocompromised hosts. The immune status of the host plays a critical role in determining the length and severity of the disease. Dehydroepiandrosterone (DHEA) is an immunomodulator that has been demonstrated to upregulate immune parameters. Ten aged (20-24 mo) Syrian golden hamsters were treated with DHEA for 7 days prior to intragastric inoculation with 1 x 10(6) C. parvum oocysts. An additional 10 aged hamsters were infected similarly but retained as untreated controls. The untreated hamsters presented with generalized infections as determined by oocyst shedding in the feces and parasite colonization of the small intestine. Hamsters treated with DHEA exhibited a significant reduction in cryptosporidial infection when compared to untreated hamsters. These results suggest that DHEA may be an effective prophylactic agent for cryptosporidiosis in immunocompromised patients.