Zisman D A, Kunkel S L, Strieter R M, Tsai W C, Bucknell K, Wilkowski J, Standiford T J
Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0360, USA.
J Clin Invest. 1997 Jun 15;99(12):2832-6. doi: 10.1172/JCI119475.
The overzealous production of proinflammatory cytokines in sepsis can result in shock, multiorgan dysfunction, and even death. In this study, we assessed the role of monocyte chemoattractant protein-1 (MCP-1) as a mediator of sepsis in endotoxin-challenged mice. Intraperitoneal administration of LPS to CD-1 mice induced a substantial time-dependent increase in MCP-1 in plasma, lung, and liver. The passive immunization of mice with rabbit antimurine MCP-1 antiserum 2 h before endotoxin administration resulted in a striking increase in LPS-induced mortality from 10% in control animals to 65% in anti-MCP-1-treated animals. Importantly, the administration of anti-MCP-1 antibodies to endotoxin-challenged mice resulted in increases in peak TNF-alpha and IL-12 levels, and also in a trend toward decreased serum levels of IL-10. Conversely, the administration of recombinant murine MCP-1 intraperitoneally significantly protected mice from endotoxin-induced lethality, and resulted in an increase in IL-10 levels, a decrease in IL-12 levels, and a trend toward decreased levels of TNF. In conclusion, our findings indicate that MCP-1 is a protective cytokine expressed in murine endotoxemia, and does so by shifting the balance in favor of antiinflammatory cytokine expression in endotoxin-challenged animals.
脓毒症中促炎细胞因子的过度产生可导致休克、多器官功能障碍甚至死亡。在本研究中，我们评估了单核细胞趋化蛋白-1（MCP-1）作为内毒素攻击小鼠脓毒症介质的作用。给CD-1小鼠腹腔注射脂多糖（LPS）可导致血浆、肺和肝脏中MCP-1随时间显著增加。在内毒素给药前2小时用兔抗鼠MCP-1抗血清对小鼠进行被动免疫，导致LPS诱导的死亡率显著增加，从对照动物的10%增至抗MCP-1处理动物的65%。重要的是，给内毒素攻击的小鼠注射抗MCP-1抗体导致肿瘤坏死因子-α（TNF-α）和白细胞介素-12（IL-12）峰值水平升高，且血清IL-10水平有降低趋势。相反，腹腔注射重组鼠MCP-1可显著保护小鼠免受内毒素诱导的致死性，并导致IL-10水平升高、IL-12水平降低以及TNF水平有降低趋势。总之，我们的研究结果表明，MCP-1是在小鼠内毒素血症中表达的一种保护性细胞因子，其通过在内毒素攻击的动物中使平衡向有利于抗炎细胞因子表达的方向转变来发挥作用。
