Immunocompromise after a major injury is presumed to be a predisposing factor for sepsis. Mice subjected to sublethal cecal ligation and puncture (CLP) and challenged 5 days later with Pseudomonas aeruginosa had more bacterial growth in lung tissue, lower serum interferon gamma (IFN-gamma) and interleukin (IL) 12,and higher serum IL-10 when compared with sham CLP mice challenged with Pseudomonas. To test the functional significance of these alterations in cytokine production in the immune response to bacteria, we administered IFN-gamma and anti-IL-10 to post-CLP mice before the Pseudomonas challenge. Administration of IFN-gamma and anti-IL-10 did not improve bacterial clearance or mortality in post-CLP mice. In further studies, we administered IFN-gamma to IL-10 knockout mice before a challenge with P. aeruginosa. Our results showed no significant differences in bacterial clearance or mortality in IL-10 knockout mice with or without IFN-gamma treatment compared with wild-type controls. Finally, because most mortality occurred within 2 to 3 days of the Pseudomonas challenge in the aforementioned studies and was likely associated with a marked proinflammatory response, we investigated the effect of IFN-gamma and anti-IL-10 on clearance of Pseudomonas in C3H/HeJ mice, which do not mount an exaggerated proinflammatory response to endotoxin or Gram-negative bacteria. Neither clearance of the Pseudomonas bacteria nor mortality was improved in C3H/HeJ mice receiving anti-IL-10 and IFN-gamma. These results suggest that the suppressed IFN-gamma and IL-12 responses, in combination with an exaggerated IL-10 response to P. aeruginosa challenge after injury, do not correlate with bacterial clearance or survival.

译文

重大损伤后的免疫损害被认为是败血症的诱发因素。与假单胞菌相比,接受亚致死性盲肠结扎和穿刺 (CLP) 并在5天后用铜绿假单胞菌攻击的小鼠肺组织中细菌生长更多,血清干扰素 γ (IFN-γ) 和白介素 (IL) 12降低,血清IL-10更高。为了测试这些细胞因子产生变化在对细菌的免疫反应中的功能意义,我们在假单胞菌攻击之前对CLP后小鼠施用IFN-γ 和anti-IL-10。施用IFN-γ 和anti-IL-10不会改善CLP后小鼠的细菌清除率或死亡率。在进一步的研究中,我们在用铜绿假单胞菌攻击之前对IL-10基因敲除小鼠施用IFN-γ。我们的结果表明,与野生型对照相比,有或没有IFN-γ 处理的IL-10基因敲除小鼠的细菌清除率或死亡率没有显着差异。最后,由于大多数死亡率发生在上述研究中假单胞菌攻击的2至3天内,并且可能与明显的促炎反应有关,因此我们研究了IFN-γ 和anti-IL-10对C3H/HeJ小鼠中假单胞菌清除的影响,它们不会对内毒素或革兰氏阴性细菌产生夸张的促炎反应。在接受anti-IL-10和IFN-γ 的C3H/HeJ小鼠中,假单胞菌的清除率和死亡率均未改善。这些结果表明,受抑制的IFN-γ 和IL-12反应,再加上损伤后对铜绿假单胞菌攻击的过度IL-10反应,与细菌清除或存活无关。

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