Sedegah M, Finkelman F, Hoffman S L
Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607.
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10700-2. doi: 10.1073/pnas.91.22.10700.
Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of rIL-122 days before challenge protected 100% of BALB/c mice against challenge with 10(2) Plasmodium yoelii sporozoites. rIL-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. rIL-12 protected BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined immunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic parasites by stimulating nitric oxide production. If rIL-12 proves to be well tolerated by humans, our findings support consideration of rIL-12 as an immunoprophylactic against malaria.
在子孢子攻击前1至2天开始，以30纳克/天的剂量腹腔注射重组白细胞介素12（rIL-12），持续5天，或者在攻击前2天给予150纳克的单剂量rIL-12，可使100%的BALB/c小鼠免受10(2) 约氏疟原虫子孢子的攻击。通过给予抗干扰素γ单克隆抗体，所有小鼠体内由rIL-12诱导的保护作用均被消除；而通过给予一氧化氮合酶竞争性抑制剂NG-单甲基-L-精氨酸，50%的小鼠体内该保护作用被消除。rIL-12对用细胞毒性抗CD4和抗CD8单克隆抗体处理过的BALB/c小鼠以及T细胞和B细胞缺陷的严重联合免疫缺陷小鼠均有保护作用。这些数据表明，rIL-12刺激非B、非T细胞产生干扰素γ，后者通过刺激一氧化氮的产生来杀死肝内寄生虫。如果rIL-12被证明对人类耐受性良好，我们的研究结果支持将rIL-12作为疟疾免疫预防药物的考虑。
