INABILITY OF INTERFERON-GAMMA AND AMINOGUANIDINE TO ALTER CRYPTOSPORIDIUM-PARVUM INFECTION IN MICE WITH SEVERE COMBINED IMMUNODEFICIENCY

Severe combined immunodeficiency (scid) mice have been useful in ident ifying specific host defense systems responsible for containing and er adicating Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts and treated weekly with monoclonal antimurine inter feron-gamma (anti-IFN-gamma). Anti-IFN-gamma-treated mice had more cry ptosporidia seen in the intestines and had more severe morphologic cha nges associated with disease than control mice. To assess the mechanis m of this effect, infected adult BALB/c and scid mice were treated wit h the nitric oxide synthase inhibitor, aminoguanidine. Infection in am inoguanidine-treated mice was not significantly different from that in control mice. Next, the effects of pharmacologic doses of IFN-gamma ( 10,000 IU) on the course of cryptosporidiosis in newborn scid mice wer e evaluated. IFN-gamma did not reverse the initial susceptibility of n eonatal scid mice to cryptosporidiosis and continued treatment with IF N-gamma (10,000 IU weekly) did not alter survival. We conclude that IF N-gamma does not exert its anticryptosporidial effect by stimulation o f nitric oxide production. Deficient IFN-gamma production by neonatal lymphocytes does not appear to be responsible for the increased severi ty of infection observed in neonatal animals. Also, IFN-gamma may not be useful in treating immunocompromised patients with cryptosporidiosi s.