Murray H W, Berman J D, Wright S D
Division of Infectious Diseases, Cornell University, Medical College, New York, New York 10021.
J Infect Dis. 1988 May;157(5):973-8. doi: 10.1093/infdis/157.5.973.
To determine if the macrophage-activating T cell lymphokine gamma interferon (IFN-gamma) can enhance the effect of conventional chemotherapy against intracellular Leishmania donovani, we treated human macrophages in vitro with both recombinant (r) IFN-gamma and sodium stibogluconate (Pentostam). After pretreatment with a nonactivating dose of rIFN-gamma (10 U/mL), ineffective concentrations of Pentostam (1 and 5 micrograms/mL) were converted to leishmanistatic concentrations, and a leishmanistatic dose (10 micrograms/mL) was converted to uptake of Pentostam. In a model of visceral leishmaniasis, infected mice were treated with ineffective concentrations of rIFN-gamma (10(4) U) plus suboptimal doses of Pentostam (10 or 50 mg/kg). With combination therapy, the doses of Pentostam required to achieve 50% inhibition or killing of visceral L. donovani were reduced by 10-fold and fourfold, respectively. These results suggest that IFN-gamma therapy may be a useful adjunct in visceral leishmaniasis and illustrate one potential role for IFN-gamma in the treatment of systemic intracellular infections.
为了确定巨噬细胞激活型T细胞淋巴因子γ干扰素（IFN-γ）是否能增强传统化疗对细胞内杜氏利什曼原虫的作用，我们在体外使用重组（r）IFN-γ和葡萄糖酸锑钠（喷他脒）处理人巨噬细胞。用非激活剂量的rIFN-γ（10 U/mL）预处理后，无效浓度的喷他脒（1和5 μg/mL）转变为抑虫浓度，而抑虫剂量（10 μg/mL）转变为喷他脒摄取量。在内脏利什曼病模型中，用无效浓度的rIFN-γ（10⁴ U）加次优剂量的喷他脒（10或50 mg/kg）治疗感染小鼠。联合治疗时，实现对内脏杜氏利什曼原虫50%抑制或杀灭所需的喷他脒剂量分别降低了10倍和4倍。这些结果表明，IFN-γ治疗可能是内脏利什曼病的一种有用辅助治疗方法，并说明了IFN-γ在治疗全身性细胞内感染中的一种潜在作用。
