Chang H R, Grau G E, Pechère J C
Department of Microbiology, University of Geneva Medical School, Switzerland.
Immunology. 1990 Jan;69(1):33-7.
Mice lethally infected with the C56 strain of Toxoplasma gondii and treated with purified recombinant murine tumour necrosis factor (TNF, 1 microgram/day/mouse for 8 days), recombinant human interleukin-1 (IL-1 alpha or IL-1 beta, 100 ng/day/mouse for 5 days) or a single dose of a combination of TNF (1 microgram/mouse) and IL-1 alpha or IL-1 beta (100 ng/mouse) were significantly protected against death (P less than 0.05-0.001, as compared with untreated infected controls). Mice infected with 100,000 tachyzoites of the highly virulent RH strain of T. gondii released serum TNF in relation to the time after infection and were primed to secrete an enhanced level of serum TNF upon stimulation with bacterial lipopolysaccharide (LPS). In vitro studies showed that interferon-gamma (IFN-gamma) increased the antimicrobial activity of murine peritoneal macrophages whereas TNF, IL-1 alpha and IL-1 beta did not. TNF, however, synergized with the anti-toxoplasmic effect provided by IFN-gamma and this activity was blocked by anti-TNF antibodies. IFN-gamma induced the production of TNF and the anti-toxoplasmic effect provided by IFN-gamma seemed to be dependent partly on the production of TNF. We conclude that TNF and IL-1 may play a significant role in modulating the host's immune defence against T. gondii infection.
用纯化的重组鼠肿瘤坏死因子（TNF，每天每只小鼠1微克，共8天）、重组人白细胞介素-1（IL-1α或IL-1β，每天每只小鼠100纳克，共5天）或单剂量的TNF（每只小鼠1微克）与IL-1α或IL-1β（每只小鼠100纳克）联合治疗的、被刚地弓形虫C56株致死感染的小鼠，对死亡有显著的保护作用（与未治疗的感染对照组相比，P<0.05 - 0.001）。感染100,000个刚地弓形虫高毒力RH株速殖子的小鼠，血清TNF的释放与感染后的时间有关，并且在用细菌脂多糖（LPS）刺激后，被激发分泌更高水平的血清TNF。体外研究表明，干扰素-γ（IFN-γ）增加了鼠腹膜巨噬细胞的抗菌活性，而TNF、IL-1α和IL-1β则没有。然而，TNF与IFN-γ提供的抗弓形虫效应协同作用，并且这种活性被抗TNF抗体阻断。IFN-γ诱导TNF的产生，并且IFN-γ提供的抗弓形虫效应似乎部分依赖于TNF的产生。我们得出结论，TNF和IL-1可能在调节宿主对刚地弓形虫感染的免疫防御中起重要作用。
