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 identifying specific host defense systems responsible for containing and eradicating Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts and treated weekly with monoclonal antimurine interferon-gamma (anti-IFN-gamma). Anti-IFN-gamma-treated mice had more cryptosporidia seen in the intestines and had more severe morphologic changes associated with disease than control mice. To assess the mechanism of this effect, infected adult BALB/c and scid mice were treated with the nitric oxide synthase inhibitor, aminoguanidine. Infection in aminoguanidine-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 were evaluated. IFN-gamma did not reverse the initial susceptibility of neonatal scid mice to cryptosporidiosis and continued treatment with IFN-gamma (10,000 IU weekly) did not alter survival. We conclude that IFN-gamma does not exert its anticryptosporidial effect by stimulation of nitric oxide production. Deficient IFN-gamma production by neonatal lymphocytes does not appear to be responsible for the increased severity of infection observed in neonatal animals. Also, IFN-gamma may not be useful in treating immunocompromised patients with cryptosporidiosis.
Kuhls
T L
TL
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
Mosier
D A
DA
Abrams
V L
VL
Crawford
D L
DL
Greenfield
R A
RA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D003457:Cryptosporidiosis / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D011897:Random Allocation; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000276:immunology*
D006146:Guanidines; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine