title: IL-12 protects immunocompetent and immunodeficient neonatal mice against infection with Cryptosporidium parvum.
abstract: The protozoan parasite Cryptosporidium parvum (Cp) causes diarrhea that can be acutely severe in immunocompetent persons and can become chronic and life-threatening in immunocompromised individuals. Because studies in mice have implicated IFN-gamma in protection against this parasite, and IL-12 can induce IFN-gamma production, we examined the ability of IL-12 to prevent or cure Cp infection in neonatal BALB/c and SCID mice. Treatment of both immunocompetent and immunodeficient mice with IL-12 before experimental inoculation with Cp oocysts prevented or greatly reduced the severity of infection. Intestinal epithelial cell invasion and/or early intracellular development of Cp was inhibited by exogenous IL-12. The protective effect of IL-12 was completely blocked by anti-IFN-gamma mAb. Established infections were associated with elevated IFN-gamma gene expression and were not ameliorated by IL-12 treatment, even though such treatment further enhanced IFN-gamma gene expression. The severity of Cp infection was, however, exacerbated by treatment with anti-IL-12 Ab. These observations provide the first evidence that treatment with exogenous IL-12 can prevent Cp infection through an IFN-gamma-dependent, specific immune system-independent mechanism, and that endogenous IL-12 production has a role in limiting Cp infection.
authors.affiliation: Parasite Immunobiology Laboratory, United States Department of Agriculture, Beltsville, MD 20705, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Urban
authors.forename: R
authors.initials: R
authors.lastname: Fayer
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: W C
authors.initials: WC
authors.lastname: Gause
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: F D
authors.initials: FD
authors.lastname: Finkelman
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D003049:Coccidiostats / Q000627:therapeutic use*; D003457:Cryptosporidiosis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D003049:Coccidiostats; D018664:Interleukin-12; D007371:Interferon-gamma