Reed S G
Seattle Biomedical Research Institute, WA 98109.
J Immunol. 1988 Jun 15;140(12):4342-7.
Recombinant murine IFN-gamma (rMu-IFN-gamma) was demonstrated to be a potent in vivo activator of mouse peritoneal macrophages to kill Trypanosoma cruzi in vitro and to be capable of conferring protection against death from acute T. cruzi infection. Following i.p. injections of rMu-IFN-gamma, resident peritoneal macrophages were cultured and infected with T. cruzi in vitro. Numbers of intracellular parasites were determined at different times thereafter. Ten or 100 micrograms (1 microgram = 6.5 X 10(5) U) of Mu-IFN-gamma, injected both 24 and 4 h before macrophage harvest, induced up to 99% inhibition of T. cruzi. One microgram of rMu-IFN-gamma was not effective under these conditions. In vitro inhibition of T. cruzi by peritoneal macrophages occurred by 24 h after infection and continued until at least 120 h after infection. There were no significant differences in initial parasite uptake by macrophages from IFN-gamma-treated or control mice, indicating that the rMu-IFN-gamma induced parasite killing. One i.p. dose of 10 micrograms was as effective as two doses if the single injection was given 24 h before macrophage harvest. In subsequent experiments, mice were given multiple injections of 10 micrograms rMu-IFN-gamma beginning 24 h before or 2 h after infection with virulent T. cruzi. Mice treated with rMu-IFN-gamma had significantly lower parasitemias and decreased morbidity compared with control mice. Proliferative responses to Con A and antibody responses to SRBC were not significantly lowered in IFN-gamma-treated mice, in contrast to untreated infected controls. All of the IFN-gamma-treated mice survived acute T. cruzi infection, whereas 100% of saline-treated infected mice died. It was demonstrated in this study that rMu-IFN-gamma activated mouse macrophages in vivo to kill T. cruzi and that rMu-IFN-gamma significantly reduced morbidity and immune suppression, and eliminated mortality resulting from acute infection with this parasite.
重组鼠干扰素-γ（rMu-IFN-γ）被证明是一种有效的体内激活剂，可激活小鼠腹腔巨噬细胞，使其在体外杀死克氏锥虫，并能够提供保护，防止死于急性克氏锥虫感染。腹腔注射rMu-IFN-γ后，培养驻留腹腔巨噬细胞并在体外感染克氏锥虫。此后在不同时间测定细胞内寄生虫的数量。在收获巨噬细胞前24小时和4小时注射10或100微克（1微克 = 6.5×10⁵单位）的Mu-IFN-γ，可诱导高达99%的克氏锥虫抑制率。在这些条件下，1微克rMu-IFN-γ无效。腹腔巨噬细胞对克氏锥虫的体外抑制在感染后24小时出现，并持续到至少感染后120小时。来自干扰素-γ处理组或对照组小鼠的巨噬细胞对初始寄生虫的摄取没有显著差异，表明rMu-IFN-γ诱导了寄生虫杀伤。如果在收获巨噬细胞前24小时进行单次注射，10微克的腹腔注射剂量与两次注射的效果相同。在随后的实验中，从感染强毒克氏锥虫前24小时或感染后2小时开始，给小鼠多次注射10微克rMu-IFN-γ。与对照小鼠相比，用rMu-IFN-γ处理的小鼠寄生虫血症显著降低，发病率降低。与未处理的感染对照组相比，干扰素-γ处理组小鼠对刀豆蛋白A的增殖反应和对绵羊红细胞的抗体反应没有显著降低。所有接受干扰素-γ处理的小鼠都在急性克氏锥虫感染中存活下来了，而100%接受生理盐水处理的感染小鼠死亡。本研究表明，rMu-IFN-γ在体内激活小鼠巨噬细胞以杀死克氏锥虫，并且rMu-IFN-γ显著降低发病率和免疫抑制，并消除了由这种寄生虫急性感染导致的死亡率。
