Diminished bacterial clearance is associated with decreased IL-12 and interferon-γ production but a sustained proinflammatory response in a murine model of postseptic immunosuppression
Diminished bacterial clearance is associated with decreased IL-12 and interferon-γ production but a sustained proinflammatory response in a murine model of postseptic immunosuppression
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DOI：
10.1097/00024382-200405000-00004
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发表时间：
2004-05-01
期刊：
影响因子：
3.1
通讯作者：
Sherwood, ER
中科院分区：
文献类型：
--
作者：
Murphey, ED;Lin, CY;Sherwood, ER
在重大疾病或损伤后，重症患者的免疫状态可能在显著的促炎反应和免疫抑制状态之间波动。炎症后免疫抑制可导致感染易感性增加。细胞因子产生的改变，如IFN γ的抑制和抗炎细胞因子IL-10的升高，被认为有助于炎症后免疫抑制。我们研究了抗微生物免疫的小鼠，以前进行了亚致死盲肠结扎和穿刺（CLP）作为模型的重大损伤。用铜绿假单胞菌（5 X 10（7）CFU i. v.）在CLP或假手术后第5天。CLP后小鼠的细菌清除受损，并与假单胞菌攻击早期应答中IFN γ产生减少和IL-10产生增加相关。假单胞菌诱导的IFN γ诱导因子IL-12的产生在CLP后小鼠中也减少。然而，CLP后小鼠的脾细胞对IFN γ诱导的细胞因子IL-12、IL-15和IL-18的外源性刺激以及T细胞受体活化仍有反应。此外，与铜绿假单胞菌攻击后的假手术小鼠相比，CLP后组的促炎细胞因子TNF-α、IL-1 β和IL-6的产生同样高，甚至更高。IL-10的阻断不能逆转CLP后小鼠脾细胞中的IL-12和IFN γ抑制。这些研究表明，CLP后小鼠中抑制的细菌清除与IFN γ和IL-12的产生减少以及IL-10和促炎细胞因子的产生增加相关。
After a major illness or injury, immune status in critically ill patients may fluctuate between a marked proinflammatory response and an immunosuppressed state. Postinflammatory immunosuppression can result in increased susceptibility to infection. Alterations of cytokine production, such as suppression of IFNgamma and elevation of the anti-inflammatory cytokine IL-10, are believed to contribute to postinflammatory immunosuppression. We examined antimicrobial immunity in mice that had previously been subjected to a sublethal cecal ligation and puncture (CLP) as a model of major injury. Mice were challenged with Pseudomonas aeruginosa (5 x 10(7) CFU i.v.) on day 5 after CLP or sham surgery. Bacterial clearance in mice after CLP was impaired and associated with decreased production of IFNgamma and increased production of IL-10 in the early response to the Pseudomonas challenge. Pseudomonas-induced production of the IFNgamma-inducing factor IL-12 was also decreased in post-CLP mice. However, splenocytes from post-CLP mice remained responsive to exogenous stimulation with the IFNgamma-inducing cytokines IL-12, IL-15, and IL-18 as well as T-cell receptor activation. Furthermore, production of the proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 were as high, or higher, in the post-CLP group compared with sham mice after P. aeruginosa challenge. Blockade of IL-10 did not reverse IL-12 and IFNgamma suppression in splenocytes from post-CLP mice. These studies show that suppressed bacterial clearance in post-CLP mice is associated with decreased production of IFNgamma and IL-12 and with increased production of IL-10 and proinflammatory cytokines.