Cannon J G, Tatro J B, Reichlin S, Dinarello C A
J Immunol. 1986 Oct 1;137(7):2232-6.
The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide alpha-melanocyte-stimulating hormone (alpha MSH). The minimal effective concentration of alpha MSH was 10(-11) M. Maximal effect occurred between 10(-8) and 10(-7) M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by alpha MSH with a biphasic dose response. The minimal effective concentration was 10(-11) M, and maximum effect was achieved at 10(-10) M. alpha MSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by alpha MSH. An analog of alpha MSH (Nle4, D-Phe7 alpha MSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of alpha MSH may not be mediated by the classic melanocyte alpha MSH receptor. The influence of alpha MSH on thymocytes and fibroblasts suggests that alpha MSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.
神经肽α-黑素细胞刺激素（α-MSH）可剂量依赖性地抑制白细胞介素1（IL-1）在体外增强小鼠胸腺细胞增殖的能力。α-MSH的最小有效浓度为10^(-11)M。最大效应出现在10^(-8)至10^(-7)M之间，浓度更高时效果逐渐减弱。α-MSH还以双相剂量反应抑制IL-1诱导的成纤维细胞产生前列腺素E（PGE）。最小有效浓度为10^(-11)M，在10^(-10)M时达到最大效应。α-MSH似乎以特定方式影响IL-1与其靶细胞的相互作用，因为它不抑制基础促有丝分裂原诱导的胸腺细胞增殖或IL-2诱导的细胞毒性T淋巴细胞系的增殖。此外，α-MSH不影响内毒素刺激的单核细胞产生IL-1。α-MSH的类似物（Nle4，D-Phe7α-MSH）在其他黑素细胞刺激素敏感系统中具有高效力，但不影响IL-1对胸腺细胞的作用，这表明α-MSH的免疫调节作用可能不是由经典的黑素细胞α-MSH受体介导的。α-MSH对胸腺细胞和成纤维细胞的影响表明，α-MSH是IL-1的内源性拮抗剂，可能对限制宿主组织的炎症损伤很重要。
