Kuhls T L, Mosier D A, Abrams V L, Crawford D L, Greenfield R A
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
J Parasitol. 1994 Jun;80(3):480-5.
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.
严重联合免疫缺陷（scid）小鼠在确定负责控制和根除微小隐孢子虫感染的特定宿主防御系统方面很有用。给成年scid小鼠接种微小隐孢子虫卵囊，并每周用单克隆抗小鼠干扰素-γ（抗IFN-γ）进行治疗。与对照小鼠相比，接受抗IFN-γ治疗的小鼠肠道内可见更多的隐孢子虫，且与疾病相关的形态学变化更严重。为了评估这种效应的机制，用一氧化氮合酶抑制剂氨基胍对受感染的成年BALB/c和scid小鼠进行治疗。氨基胍治疗小鼠的感染情况与对照小鼠无显著差异。接下来，评估了药理剂量的IFN-γ（10,000 IU）对新生scid小鼠隐孢子虫病病程的影响。IFN-γ并未逆转新生scid小鼠对隐孢子虫病的初始易感性，持续用IFN-γ（每周10,000 IU）治疗也未改变生存率。我们得出结论，IFN-γ并非通过刺激一氧化氮的产生来发挥其抗隐孢子虫作用。新生淋巴细胞产生IFN-γ不足似乎不是新生动物感染严重程度增加的原因。此外，IFN-γ可能对治疗患有隐孢子虫病的免疫受损患者无用。
