Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.
Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.
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DOI：
10.4049/jimmunol.155.2.722
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发表时间：
1995-07
影响因子：
4.4
通讯作者：
M. Greenberger;R. Strieter;S. Kunkel;J. Danforth;R. Goodman;T. Standiford
中科院分区：
文献类型：
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作者：
M. Greenberger;R. Strieter;S. Kunkel;J. Danforth;R. Goodman;T. Standiford
针对细菌感染的有效宿主防御依赖于中性粒细胞和巨噬细胞的大力募集和激活。我们假设IL-10是在细菌性肺炎的背景下产生的，这种细胞因子可能通过抑制重要的活化性和趋化性细胞因子的表达来减弱宿主防御。CD-1小鼠气管内注射30微升生理盐水或含有10(3)cfu肺炎克雷伯氏菌的生理盐水(I.T.)。分别于8、24、48h取肺组织。接种肺炎克雷伯菌后，肺组织匀浆中的肿瘤坏死因子、巨噬细胞炎性蛋白-2和巨噬细胞炎性蛋白-1α的水平分别是对照组的13、14和8倍。此外，我们还观察到肺组织匀浆中IL-10mRNA和蛋白水平的增加，在接种后48小时达到最高水平。为确定IL-10在肺炎克雷伯菌中的生物学意义，我们用0.5ml兔抗鼠IL-10血清或免疫前血清ip被动免疫CD-1小鼠。I.T.前2小时。肺炎克雷伯菌的给药。与免疫前相比，IL-10抗血清处理后24小时和48小时肺组织匀浆中的肿瘤坏死因子、MIP-2和MIP-1α水平分别升高。此外，中和IL-10可显著降低48h肺组织匀浆和血浆中肺炎克雷伯菌的菌落数，显著提高动物的存活率。我们的研究表明：1)肺炎克雷伯菌产生IL-10；2)体内抑制IL-10生物活性会导致细菌清除增强，促炎细胞因子表达增加，从而延长生存时间。
Effective host defense against bacterial infection is dependent upon the vigorous recruitment and activation of neutrophils and macrophages. We hypothesized that IL-10 is produced in the setting of bacterial pneumonia, and this cytokine may attenuate host defense by inhibiting the expression of important activating and chemotactic cytokines. CD-1 mice were challenged with either 30 microliters of saline or saline containing 10(3) CFUs of Klebsiella pneumoniae intratracheally (i.t.) and lungs were harvested at 8, 24, and 48 h. The i.t. inoculation with K. pneumoniae resulted in a 13-, 14-, and 8-fold increase in lung homogenate TNF, macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) levels, respectively, as compared with control animals. In addition, we observed an increase in IL-10 mRNA and protein levels in lung homogenates, maximal at 48 h postinoculation. To establish the biologic relevance of IL-10 in Klebsiella pneumonia, we passively immunized CD-1 mice with 0.5 ml of rabbit anti-murine IL-10 serum or preimmune serum i.p. 2 h before i.t. administration of K. pneumoniae. Treatment of animals with anti-IL-10 serum resulted in increased levels of TNF, MIP-2, and MIP-1 alpha, respectively, within lung homogenates at 24 and 48 h, as compared with preimmune-treated animals. Furthermore, neutralization of IL-10 resulted in a significant decrease in K. pneumoniae CFU in both lung homogenates and plasma harvested at 48 h, as well as a significant increase in survival in these animals. Our studies indicate that 1) IL-10 is produced during Klebsiella pneumonia; and 2) inhibition of IL-10 bioactivity in vivo results in enhanced bacterial clearance, increased expression of proinflammatory cytokines, and prolonged survival.