Peptide modulation of fever and inflammation within the brain
Peptide modulation of fever and inflammation within the brain
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DOI：
10.1111/j.1749-6632.1998.tb08313.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Lipton, JM
中科院分区：
文献类型：
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作者：
Catania, A;Lipton, JM
黑皮质素肽对宿主反应的重要性通过观察集中施用的α-黑素细胞刺激激素（α-MSH）的解热作用而被认识到。现在清楚的是，这种神经肽还通过直接作用于外周宿主细胞、源自CNS黑皮质素受体的下行神经源性促黑激素途径以及对控制脑内炎症的受体的局部作用而发挥显著的促黑激素活性。最近对后者影响的研究表明，α-MSH抑制脑肿瘤坏死因子-α脑缺血/再灌注，中风模型，诱导以CNS功能紊乱为标志的炎症，全身给予的α-MSH调节由后循环中的缺血/再灌注诱导的听觉诱发电位的紊乱。肽的这种影响可能通过抑制神经胶质产生的炎症因子而发生：α-MSH 1-13和11-13调节由活化的鼠小胶质细胞产生的TNF-α和一氧化氮，以及由人星形胶质细胞产生的TNF-α。因为胶质细胞可以分泌α-MSH并表达黑皮质素受体，所以它们可以像外周巨噬细胞一样含有基于肽的自分泌调节回路，因此，α-MSH通过作用于局部黑皮质素受体来调节脑中的发热和炎症。
The importance of melanocortin peptides to host responses was recognized with the observation of the antipyretic effect of centrally administered alpha-melanocyte stimulating hormone (alpha-MSH). It is now clear that this neuropeptide also exerts remarkable antiinflammatory activity via direct actions on peripheral host cells, descending neurogenic antiinflammatory pathways stemming from CNS melanocortin receptors, and local actions on receptors that control inflammation within the brain, Recent studies of the latter influence indicate that alpha-MSH inhibits brain tumor necrosis factor-alpha (TNF-alpha), previously linked to human neurodegenerative diseases, induced by local injection of lipopolysaccharide, Ischemia/reperfusion of the brain, a model of stroke, induces inflammation marked by disturbance of CNS function, alpha-MSH given systemically modulates disturbances of auditory evoked potentials induced by ischemia/reperfusion in the posterior circulation. Such influences of the peptide may occur through inhibition of inflammatory agents produced by glia: alpha-MSH 1-13 and 11-13 modulate TNF-alpha and nitric oxide produced by activated murine microglia, and TNF-alpha produced by human astrocytes, Because glia can secrete alpha-MSH and express melanocortin receptors, they may, like peripheral macrophages, contain autocrine regulatory circuits based on the peptide, alpha-MSH thus modulates both fever and inflammation in the brain by acting on local melanocortin receptors.