Curfs J H, van der Meide P H, Billiau A, Meuwissen J H, Eling W M
Department of Medical Microbiology, Catholic University of Nijmegen, The Netherlands.
Exp Parasitol. 1993 Sep;77(2):212-23. doi: 10.1006/expr.1993.1078.
Mice infected with Plasmodium berghei K173-parasitized erythrocytes develop severe hypothermia followed by death as a consequence of murine cerebral malaria early in the second week after infection. A single intraperitoneal injection of 10(5) Units of IFN-gamma given between Day 4 and Day 6 postinfection results in a transient decrease of body temperature. No effect on parasitemia and cerebral malaria is obtained by this treatment. Daily injections of relatively low doses of IFN-gamma delays the patency of the infection for 2 days. Furthermore the proliferation rate of the parasites is reduced and the development of cerebral malaria is also delayed for 2 days. The reduction of body temperature, as found in untreated infected mice, is absent. Administration of IFN-gamma by means of a continuous delivery from intraperitoneally inserted osmotic pumps (1.2 x 10(4) Units of IFN-gamma/24 hr) also delays patency and inhibits parasitemia. Body temperature decreases during infection but mice are protected against the development of cerebral malaria. In nude mice, this treatment inhibits parasitemia to the same extent. However, reduction of body temperature was also prevented. High doses of IFN-gamma delivered by osmotic pumps (2.5 x 10(4) or 10(5) Units of IFN-gamma/24 hr) appear to be lethally toxic in conventional as well as in nude mice, independently of infection. Cerebral malaria-like symptoms are found in these mice. Treatment of infected C57BL/6J mice with antibody to IFN-gamma 4 days before and after infection as well as on the day of infection enhances parasitemia but does not affect the development of murine cerebral malaria. Single injections of anti-IFN-gamma-antibody 6 hr prior to infection or 7 days after infection have no effect. In CBA/Ca mice, treatment with anti-IFN-gamma-antibody enhances parasitemia; furthermore protection against cerebral malaria was obtained in part of the mice.
感染了伯氏疟原虫K173寄生红细胞的小鼠，在感染后第二周早期会因鼠脑型疟疾而出现严重体温过低，随后死亡。在感染后第4天至第6天之间单次腹腔注射10⁵单位的γ干扰素，会导致体温短暂下降。这种治疗对疟原虫血症和脑型疟疾没有影响。每天注射相对低剂量的γ干扰素可使感染的显露期延迟2天。此外，寄生虫的增殖率降低，脑型疟疾的发展也延迟2天。未治疗的感染小鼠中出现的体温下降情况不存在。通过腹腔内插入的渗透泵持续输送γ干扰素（1.2×10⁴单位的γ干扰素/24小时）也会延迟显露期并抑制疟原虫血症。感染期间体温下降，但小鼠受到保护，不会发展为脑型疟疾。在裸鼠中，这种治疗在相同程度上抑制疟原虫血症。然而，体温下降也得到了预防。渗透泵输送高剂量的γ干扰素（2.5×10⁴或10⁵单位的γ干扰素/24小时）在常规小鼠和裸鼠中似乎都具有致命毒性，与感染无关。在这些小鼠中发现了类似脑型疟疾的症状。在感染前后4天以及感染当天用抗γ干扰素抗体治疗感染的C57BL/6J小鼠会增加疟原虫血症，但不影响鼠脑型疟疾的发展。在感染前6小时或感染后7天单次注射抗γ干扰素抗体没有效果。在CBA/Ca小鼠中，用抗γ干扰素抗体治疗会增加疟原虫血症；此外，部分小鼠获得了针对脑型疟疾的保护。
