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

:大伤后的免疫功能低下被认为是败血症的诱因。进行半致死盲肠结扎和穿刺(CLP)并在5天后用铜绿假单胞菌攻击的小鼠的肺组织中细菌生长更多,血清干扰素-γ(IFN-γ)和白介素(IL)12更低,而血清IL-10更高。与假单胞菌攻击的假CLP小鼠相比。为了测试这些变化对细菌免疫反应中细胞因子产生的功能意义,我们在假单胞菌攻击之前向CLP后小鼠施用了IFN-γ和抗IL-10。在CLP后小鼠中,IFN-γ和抗IL-10的使用不能改善细菌清除率或死亡率。在进一步的研究中,我们在铜绿假单胞菌攻击之前向IL-10敲除小鼠施用了IFN-γ。我们的结果显示,与野生型对照相比,接受或未接受IFN-γ治疗的IL-10基因敲除小鼠的细菌清除率或死亡率无显着差异。最后,由于在上述研究中大多数死亡发生在假单胞菌攻击后的2到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和抗IL-10对C3H / 3中假单胞菌清除的影响HeJ小鼠,对内毒素或革兰氏阴性细菌没有过度的促炎反应。接受抗IL-10和IFN-γ的C3H / HeJ小鼠的假单胞菌细菌清除率和死亡率均未提高。这些结果表明,损伤后抑制的IFN-γ和IL-12反应,加上对损伤后铜绿假单胞菌攻击的过度IL-10反应,与细菌清除率或存活率无关。

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