Department of Surgery, Technical University Munich, Ismaninger Strasse 22, 81675 Munich, Germany.
Immunobiology. 2012 Aug;217(8):761-7. doi: 10.1016/j.imbio.2012.04.009. Epub 2012 May 4.
The neuropeptide CGRP contributes to the control of excessive cytokine production in endotoxemia models. However, the function of CGRP in sepsis caused by infection with viable pathogens is unknown. Here, we show that mice deficient for the CGRP receptor component RAMP1 have an improved anti-bacterial defense during the early, but not late, phase of polymicrobial septic peritonitis. The protective effect of Ramp1-deficiency was associated with reduced levels of IL-10 in plasma and peritoneal lavage fluid. Consistent with these findings, CGRP markedly increased IL-10 production of peritoneal and bone marrow-derived macrophages in response to short term stimulation with LPS in vitro. In addition, the lack of an intact CGRP receptor resulted in an increased recruitment and activation of neutrophils and caused an enhanced release of defensin-α1 in the peritoneal cavity. Considered together, our results identify the neuropeptide CGRP as a crucial immunosuppressive mediator impairing host defense during the early, but not late, phase of septic peritonitis.
降钙素基因相关肽（CGRP）有助于控制内毒素血症模型中过度的细胞因子产生。然而，在由有活力的病原体感染引起的败血症中，CGRP 的功能尚不清楚。在这里，我们表明，缺乏 CGRP 受体成分 RAMP1 的小鼠在多微生物性腹膜炎败血症的早期而非晚期具有更好的抗细菌防御能力。Ramp1 缺陷的保护作用与血浆和腹腔灌洗液中 IL-10 水平降低有关。与这些发现一致的是，CGRP 明显增加了腹腔和骨髓来源的巨噬细胞对 LPS 的短期刺激的 IL-10 产生。此外，缺乏完整的 CGRP 受体导致中性粒细胞的募集和激活增加，并导致腹腔内防御素-α1 的释放增强。综上所述，我们的研究结果表明，神经肽 CGRP 是一种关键的免疫抑制介质，在败血症性腹膜炎的早期而非晚期阶段损害宿主防御。
