Instituto de Parasitologia y Biomedicina Lopez-Neyra, Consejo Superior de Investigaciones Cientificas, Granada, Spain.
Neuroendocrinology. 2011;94(2):89-100. doi: 10.1159/000328636. Epub 2011 Jul 7.
Although necessary to eliminate pathogens, inflammation can lead to serious deleterious effects in the host if left unchecked. During the inflammatory response, further damage may arise from potential autoimmune responses occurring when the immune cells and molecules that respond to pathogen-derived antigens also react to self-antigens. In this sense, the identification of endogenous factors that control exacerbated immune responses is a key goal for the development of new therapeutic approaches for inflammatory and autoimmune diseases. Some neuropeptides that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that could collaborate in tuning the balanced steady state of the immune system. These neuropeptides participate in maintaining immune tolerance through two distinct mechanisms: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors. Indeed, a functioning neuropeptide system contributes to general health, and alterations in the levels of these neuropeptides and/or their receptors lead to changes in susceptibility to inflammatory and autoimmune diseases. Recently, we found that some neuropeptides also have antimicrobial and antiparasitic actions, suggesting that they could act as primary mediators of innate defense, even in the most primitive organisms. In this review, we use the vasoactive intestinal peptide as example of an immunomodulatory neuropeptide to summarize the most relevant data found for other neuropeptides with similar characteristics, including adrenomedullin, urocortin, cortistatin and ghrelin.
虽然消除病原体是必要的，但如果炎症不受控制，它可能会对宿主造成严重的有害影响。在炎症反应过程中，当免疫细胞和分子对病原体衍生抗原的反应也对自身抗原产生潜在的自身免疫反应时，可能会产生进一步的损伤。从这个意义上说，确定控制过度免疫反应的内源性因素是开发炎症和自身免疫性疾病新治疗方法的关键目标。一些在持续炎症反应中产生的神经肽已成为内源性抗炎剂，它们可以协同调节免疫系统的平衡稳态。这些神经肽通过两种不同的机制参与维持免疫耐受：通过调节促炎和抗炎因子之间的平衡，以及通过诱导具有抑制自身反应性 T 细胞效应器活性的调节性 T 细胞的出现。事实上，正常运作的神经肽系统有助于整体健康，这些神经肽及其受体水平的改变会导致对炎症和自身免疫性疾病的易感性发生变化。最近，我们发现一些神经肽还具有抗微生物和抗寄生虫作用，这表明它们可能作为先天防御的主要介质发挥作用，甚至在最原始的生物中也是如此。在这篇综述中，我们以血管活性肠肽为例，总结了具有类似特征的其他神经肽的最相关数据，包括肾上腺髓质素、尿皮质素、皮质抑素和生长激素释放肽。
