Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression
Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression
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DOI：
10.4049/jimmunol.170.1.503
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发表时间：
2003-01-01
影响因子：
4.4
通讯作者：
Ward, PA
中科院分区：
文献类型：
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作者：
Riedemann, NC;Neff, TA;Ward, PA
已知IL-6是重要的促炎和抗炎细胞因子，其在脓毒症期间上调。我们以前的工作表明IL-6在脓毒症中上调C5 aR中的作用。我们之前报道过，阻断C5 a或C5 aR可改善实验性脓毒症的结局。在小鼠中使用盲肠结扎/穿孔（CLP）模型，我们现在证明用抗IL-6 Ab（抗IL-6）治疗导致显著改善的存活，这取决于Ab输注的量。与0 h时的对照小鼠或输注正常兔I-125标记IgG的CLP动物相比，CLP动物显示I-125标记的抗C5 aR与器官的结合显著增加。CLP后6 h，抗IL-6处理的动物中I-125标记的抗C5 aR与肺、肝、肾和心脏的结合显著降低。CLP后3、6和12 h从不同器官中分离的mRNA的RT-PCR实验表明，脓毒症发作期间C5 aR mRNA表达增加，这在用抗IL-6治疗的CLP小鼠中被极大地抑制。这些数据表明，IL-6在小鼠脓毒症发展过程中肺、肝、肾和心脏中C5 aR表达增加中起重要作用，并且IL-6的拦截导致C5 aR表达减少和存活改善。
IL-6 is known to be an important pro- and anti-inflammatory cytokine, which is up-regulated during sepsis. Our previous work has suggested a role for IL-6 in the up-regulation of C5aR in sepsis. We reported earlier that interception of C5a or C5aR results in improved outcomes in experimental sepsis. Using the cecal ligation/puncture (CLP) model in mice, we now demonstrate that treatment with anti-IL-6 Ab (anti-IL-6) results in significantly improved survival, dependent on the amount of Ab infused. CLP animals showed significantly increased binding of I-125-labeled anti-C5aR to organs when compared to either control mice at 0 h or CLP animals infused with normal rabbit I-125-labeled IgG. Binding of I-125-labeled anti-C5aR to lung, liver, kidney, and heart was significantly decreased in anti-IL-6-treated animals 6 h after CLP. RT-PCR experiments with mRNA isolated from various organs obtained 3, 6, and 12 h after CLP demonstrated increased C5aR mRNA expression during the onset of sepsis, which was greatly suppressed in CLP mice treated with anti-IL-6. These data suggest that IL-6 plays an important role in the increased expression of C5aR in lung, liver, kidney, and heart during the development of sepsis in mice and that interception of IL-6 leads to reduced expression of C5aR and improved survival.