University-Medicine Charité, Charité Center 12 for Internal Medicine and Dermatology, D-10117 Berlin, Germany.
J Immunol. 2011 Jan 15;186(2):848-55. doi: 10.4049/jimmunol.0903878. Epub 2010 Dec 20.
Interaction between the nervous and immune systems greatly contributes to inflammatory disease. In organs at the interface between our body and the environment, the sensory neuropeptide substance P (SP) is one key mediator of an acute local stress response through neurogenic inflammation but may also alter cytokine balance and dendritic cell (DC) function. Using a combined murine allergic inflammation/noise stress model with C57BL/6 mice, we show in this paper that SP--released during repeated stress exposure--has the capacity to markedly attenuate inflammation. In particular, repeated stress exposure prior to allergen sensitization increases DC-nerve fiber contacts, enhances DC migration and maturation, alters cytokine balance, and increases levels of IL-2 and T regulatory cell numbers in local lymph nodes and inflamed tissue in a neurokinin 1-SP-receptor (neurokinin-1 receptor)-dependent manner. Concordantly, allergic inflammation is significantly reduced after repeated stress exposure. We conclude that SP/repeated stress prior to immune activation acts protolerogenically and thereby beneficially in inflammation.
神经系统和免疫系统的相互作用极大地促成了炎症性疾病。在我们身体与环境的交界处的器官中，感觉神经肽物质 P（SP）是通过神经源性炎症介导急性局部应激反应的关键介质之一，但也可能改变细胞因子平衡和树突状细胞（DC）功能。本文使用 C57BL/6 小鼠的过敏性炎症/噪声应激联合模型表明，SP——在反复应激暴露期间释放——具有显著减轻炎症的能力。特别是，在过敏原致敏前进行重复应激暴露会增加 DC-神经纤维接触，增强 DC 迁移和成熟，改变细胞因子平衡，并增加局部淋巴结和炎症组织中白细胞介素 2 和 T 调节细胞的数量，这是一种神经激肽 1-SP 受体（神经激肽-1 受体）依赖性方式。一致的是，重复应激暴露后过敏性炎症显著减轻。我们得出结论，SP/在免疫激活前的重复应激作用是免疫耐受原性的，因此对炎症有益。
