Cytokines IL-1β, IL-6, and TNF-α enhance in vitro growth of bacteria
Cytokines IL-1β, IL-6, and TNF-α enhance in vitro growth of bacteria
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DOI：
10.1164/ajrccm.160.3.9807080
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发表时间：
1999-09-01
影响因子：
24.7
通讯作者：
Schaberg, D
中科院分区：
文献类型：
--
作者：
Meduri, GU;Kanangat, S;Schaberg, D
我们以前曾报道过，在急性呼吸窘迫综合征（ARDS）中，死亡者的肺部和循环中的促炎细胞因子水平随着时间的推移而持续升高，并且死前医院感染的发生率很高。在这些患者中，没有一个被证实或怀疑的医院感染引起血浆促炎细胞因子水平短暂或持续升高超过感染前值。我们推测，在ARDS过程中，宿主分泌的细胞因子可能有利于细菌的生长。我们进行了一项体外研究，对三种与医院感染临床相关的细菌的生长进行了评价，评估了它们对不同浓度的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1 β和IL-6的体外反应。我们发现，所有三种细菌物种显示浓度依赖性的生长增强时，与一种或多种测试的细胞因子孵育，并通过特异性中和细胞因子单克隆抗体的封锁显着抑制精氨酸诱导的生长。与对照相比，对于金黄色葡萄球菌（36 +/- 16 vs 377 +/- 16; p = 0.0001）和不动杆菌属，1，000 pg II-1 β的6小时生长反应（cfu/ml）最大。(317+/-1，147对比1，124 +/- 147; p = 0.002）和对于铜绿假单胞菌，IL-6为1，000 pg（99 +/- 50对比509 +/- 50; p = 0.009）。细胞因子的作用仅见于新鲜分离株，并且在不添加细胞因子的细菌培养基上体外传代时丧失。在这项研究中，我们提供了额外的证据，一个新描述的致病机制，细菌增殖的存在夸大和旷日持久的炎症。
We have previously reported that in acute respiratory distress syndrome (ARDS), nonsurvivors have persistent elevation in pulmonary and circulating proinflammatory cytokine levels over time and a high rate of nosocomial infections antemortem. In these patients, none of the proven or suspected nosocomial infections caused a transient or sustained increase in plasma proinflammatory cytokine levels above preinfection values. We hypothesized that cytokines secreted by the host during ARDS may favor the growth of bacteria. We conducted an in vitro study of the growth of three bacteria clinically relevant in nosocomial infections, evaluating their in vitro response to various concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. We found that all three bacterial species showed concentration-dependent growth enhancement when incubated with one or more tested cytokines and that blockade by specific neutralizing cytokine MoAb significantly inhibited cytokine-induced growth. When compared with control, the 6-h growth response (cfu/ml) was maximal with II-1 beta at 1,000 pg for Staphylococcus aureus (36 +/- 16 versus 377 +/- 16; p = 0.0001) and Acinetobacter spp. (317 +/- 1,147 versus 1,124 +/- 147; p = 0.002) and with IL-6 at 1,000 pg for Pseudomonas aeruginosa (99 +/- 50 versus 509 +/- 50; p = 0.009). The effects of cytokines were seen only with fresh isolates and were lost with passage in vitro on bacteriologic medium without added cytokines. In this study we provide additional evidence for a newly described pathogenetic mechanism for bacterial proliferation in the presence of exaggerated and protracted inflammation.