Kurtz R S, Young K M, Czuprynski C J
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Infect Immun. 1989 Feb;57(2):553-8. doi: 10.1128/iai.57.2.553-558.1989.
Our laboratory has previously reported that administration of murine recombinant interleukin 1 alpha (rIL-1 alpha) substantially enhanced the resistance of mice to Listeria monocytogenes infection. Other investigators have reported that gamma interferon (IFN-gamma) plays a pivotal role in antilisteria resistance. In the present study, we have defined doses of human rIL-1 alpha that enhanced the antilisteria resistance of mice. We then addressed the possibility that combined immunotherapy with rIL-1 alpha and recombinant IFN-gamma (rIFN-gamma) might result in an additive or synergistic enhancement of antibacterial resistance. Simultaneous administration of rIL-1 alpha and rIFN-gamma enhanced antilisteria resistance (at 3 days after infection) to a greater extent than did either cytokine alone, although the results did not imply a synergistic action between the two cytokines. Experiments which examined the effects of the timing of cytokine administration indicated that maximal protection was observed when rIL-1 alpha and rIFN-gamma were administered together concomitantly with the L. monocytogenes challenge. When we compared the separate and combined protective effects of rIL-1 alpha and rIFN-gamma throughout the course of a primary L. monocytogenes infection, we observed an additive effect of the two cytokines only at 3 days after challenge, the time at which the peak bacterial burden occurs in the spleens and livers of infected mice. Histopathological comparisons of livers and spleens from cytokine-treated and control listeria-infected mice verified that cytokine treatment reduced the severity of tissue damage in cytokine-treated listeria-infected mice. In an attempt to provide a potential mechanism for the protective effects of rIL-1 alpha and rIFN-gamma administration, we compared levels of colony-stimulating activity in sera from cytokine-treated and control listeria-infected mice. The highest levels of colony-stimulating activity were detected in sera from control listeria-infected mice; somewhat lower levels were found in sera from listeria-infected mice that received rIL-1 alpha and rIFN-gamma either alone or in combination.
我们实验室先前报道，给予小鼠重组白细胞介素1α（rIL-1α）可显著增强小鼠对单核细胞增生李斯特菌感染的抵抗力。其他研究者报道，γ干扰素（IFN-γ）在抗李斯特菌感染中起关键作用。在本研究中，我们确定了可增强小鼠抗李斯特菌感染抵抗力的人rIL-1α剂量。然后我们探讨了rIL-1α与重组IFN-γ（rIFN-γ）联合免疫治疗是否可能导致抗菌抵抗力的相加或协同增强。同时给予rIL-1α和rIFN-γ比单独给予任何一种细胞因子更能增强（感染后3天）抗李斯特菌感染的抵抗力，尽管结果并不意味着这两种细胞因子之间存在协同作用。研究细胞因子给药时间影响的实验表明，当rIL-1α和rIFN-γ与单核细胞增生李斯特菌攻击同时给予时，可观察到最大程度的保护作用。当我们比较rIL-1α和rIFN-γ在原发性单核细胞增生李斯特菌感染全过程中的单独和联合保护作用时，我们发现仅在攻击后3天这两种细胞因子有相加作用，此时感染小鼠脾脏和肝脏中的细菌负荷达到峰值。对细胞因子处理组和对照组李斯特菌感染小鼠的肝脏和脾脏进行组织病理学比较证实，细胞因子处理减轻了细胞因子处理组李斯特菌感染小鼠的组织损伤严重程度。为了探寻rIL-1α和rIFN-γ给药产生保护作用的潜在机制，我们比较了细胞因子处理组和对照组李斯特菌感染小鼠血清中的集落刺激活性水平。在对照组李斯特菌感染小鼠的血清中检测到最高水平的集落刺激活性；在单独或联合接受rIL-1α和rIFN-γ的李斯特菌感染小鼠血清中发现的活性水平略低。
