INTERLEUKIN-6-DEFICIENT MICE ARE HIGHLY SUSCEPTIBLE TO LISTERIA-MONOCYTOGENES INFECTION - CORRELATION WITH INEFFICIENT NEUTROPHILIA
INTERLEUKIN-6-DEFICIENT MICE ARE HIGHLY SUSCEPTIBLE TO LISTERIA-MONOCYTOGENES INFECTION - CORRELATION WITH INEFFICIENT NEUTROPHILIA
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DOI：
10.1128/iai.63.6.2262-2268.1995
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发表时间：
1995-06-01
影响因子：
3.1
通讯作者：
MURRAY, R
中科院分区：
文献类型：
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作者：
DALRYMPLE, SA;LUCIAN, LA;MURRAY, R
我们已经产生了白细胞介素-6（IL-6）缺陷小鼠，在体内检查，各种各样的生物活性归因于这种多功能的细胞因子。为了研究IL-6在感染性疾病中的作用，用亚致死剂量的单增李斯特菌（一种兼性细胞内细菌）攻击IL-6缺陷小鼠。虽然正常对照动物能够清除感染，但突变动物表现出高死亡率，并在感染后2天和3天显示出脾脏和肝脏中细菌的不受控制的复制。感染组织的切片显示炎性病灶的数量和严重程度增加。给予重组鼠IL-6（rIL-6）后，突变动物中该表型的所有方面均完全恢复。自然杀伤（NK）细胞和巨噬细胞功能的各种参数在突变体动物的挑战不受影响。然而，IL-6缺乏的动物未能安装外周血嗜中性粒细胞反应，而对照组动物在感染后24和38小时的血液中显示出突出的嗜中性粒细胞。此外，我们分析了rIL-6在保护缺乏淋巴细胞或缺乏嗜中性粒细胞的动物中的功效。施用rIL-6对缺乏淋巴细胞的动物具有保护作用，表明rIL-6的保护作用不是通过淋巴细胞介导的。与此相反，控制和突变体动物耗尽的中性粒细胞是难治性的rIL-6的保护作用。这些数据表明，IL-6是至关重要的早期在acidriosis，可能通过刺激中性粒细胞直接或间接。此外，这些数据显示了机会性感染期间rIL-6给药的有希望的治疗潜力。
We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo, the wide variety of biological activities attributed to this multifunctional cytokine. To investigate the role of IL-6 during infectious disease, IL-6-deficient mice were challenged with sublethal doses of Listeria monocgtogenes, a facultative intracellular bacterium. While normal control animals were able to clear the infection, mutant animals exhibited a high mortality rate and showed uncontrolled replication of the bacteria in the spleen and liver at 2 and 3 days postinfection. Sections of infected tissues showed an increase in the number and severity of inflammatory foci. All aspects of this phenotype in the mutant animals were completely reverted upon administration of recombinant murine IL-6 (rIL-6). Various parameters of natural killer (NK) cell and macrophage function were unaffected in the challenge of the mutant animals. However, IL-6 deficient animals failed to mount peripheral blood neutrophilia in response to listeriosis, whereas control animals displayed a prominent neutrophilia in the blood at 24 and 38 h postinfection. Additionally, we analyzed the efficacy of rIL-6 in protecting animals devoid of lymphocytes or devoid of neutrophils during listeriosis. Administration of rIL-6 was protective to animals devoid of lymphocytes, suggesting that the rIL-6 protective effect was not mediated through lymphocytes. In contrast, control and mutant animals depleted of neutrophils were refractory to the rIL-6 protective effect. These data suggest that IL-6 is critical early during listeriosis, perhaps acting by stimulating neutrophils either directly or indirectly. Additionally, these data show a promising therapeutic potential for rIL-6 administration during opportunistic infection.