A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection.
A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection.
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DOI：
10.1073/pnas.85.5.1620
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发表时间：
1988-03
影响因子：
11.1
通讯作者：
J. Meer;M. Barza;S. Wolff;C. Dinarello
中科院分区：
文献类型：
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作者：
J. Meer;M. Barza;S. Wolff;C. Dinarello
天然和合成的免疫调节剂可以增加对感染的非特异性抵抗力，从而诱导白介素1(IL-1)的产生。因此，我们研究了给予IL-1对致死性感染的粒细胞减少症小鼠存活的影响。环磷酰胺诱导的粒细胞减少的小鼠在0时间大腿肌肉注射大约10(7)个铜绿假单胞菌；6小时和23小时后注射庆大霉素。当重组人IL-1β(IL-1的两种形式之一)作为单一ip给药时。感染前24小时注射可提高存活率。使用每只小鼠80 ng的IL-1β，与对照组动物相比，感染后24小时的存活率为98%对71%，30小时的存活率为98%对60%，36小时的存活率为86%对36%，48小时的存活率为61%对11%(P<0.001)。IL-1在感染前0.5小时或感染后6小时给药均未见明显效果。没有接受庆大霉素治疗的动物也从IL-1中受益。给予环氧合酶抑制剂布洛芬并不影响IL-1的活性。从血液、大腿肌肉、肝脏、脾和肾脏培养出的细菌数量在IL-1处理组和对照组动物中相似。两组的腹膜巨噬细胞产生的超氧阴离子也相似。这些研究表明，IL-1预处理保护粒细胞减少的小鼠免受致死性假单胞菌感染，并表明这种保护作用是通过非细胞机制发生的。
Natural and synthetic immunomodulators that increase nonspecific resistance to infection induce interleukin 1 (IL-1) production. Therefore, we investigated the effect of the administration of IL-1 on the survival of lethally infected granulocytopenic mice. Mice with cyclophosphamide-induced granulocytopenia were injected with approximately 10(7) Pseudomonas aeruginosa in the thigh muscle at time 0; gentamicin was administered 6 hr and 23 hr later. When recombinant human IL-1 beta (one of the two forms of IL-1) was given as a single i.p. injection 24 hr before the infection, survival was increased. Using 80 ng of IL-1 beta per mouse, survival compared to control animals was 98% vs. 71% at 24 hr, 98% vs. 60% at 30 hr, 86% vs. 36% at 36 hr, and 61% vs. 11% at 48 hr (P less than 0.001) after the infection. No effect of IL-1 was observed when it was given 0.5 hr before or 6 hr after the infection. Animals not treated with gentamicin also benefited from the IL-1. Administration of the cyclooxygenase inhibitor ibuprofen did not affect the activity of IL-1. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in IL-1-treated and control animals. Superoxide production by peritoneal macrophages was also similar in the two groups. These studies demonstrate that IL-1 pretreatment protects granulocytopenic mice against lethal pseudomonas infection and suggest that this protection occurs through a noncellular mechanism.