Taylor Andrew W, Kitaichi Nobuyoshi
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Brain Behav Immun. 2008 Jul;22(5):639-46. doi: 10.1016/j.bbi.2007.11.001. Epub 2008 Jan 2.
The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in immune privilege by its suppression of inflammation, and its induction of regulatory T cells. This finding led us to test the possibility that we can use alpha-MSH to suppress autoimmune diseases, and promote re-establishment of immune tolerance to autoantigens. To test this possibility, SJL mice with experimental autoimmune encephalomyelitis (EAE) were injected with alpha-MSH at the first signs of paralysis. The alpha-MSH-treated mice in comparison with untreated EAE mice had a profound diminishment in the severity and tempo of EAE. The spleen cells in alpha-MSH-treated EAE produced TGF-beta in response to PLP-antigen stimulation in contrast to untreated mice spleen cells that produced IFN-gamma. When the alpha-MSH-treated EAE mice were reimmunized there was a delay of a week before the second episode of EAE. Although this delay maybe because of the induction of TGF-beta-producing spleen cells by the alpha-MSH-treatment, it was not adequate to suppress IFN-gamma-production by PLP-antigen stimulated spleen cells from untreated mice, nor able to suppress the eventual second episode of EAE. Therefore, the injection of alpha-MSH at the onset of paralysis is extremely effective in diminishing the severity and tempo of EAE, and the subsequent induction of potential PLP-specific Treg cells suggests that an alpha-MSH therapy could be attempted as part of a therapeutic regiment to impose immunoregulation and immunosuppression on an autoimmune disease of the central nervous system.
神经肽α-黑素细胞刺激素（α-MSH）通过抑制炎症和诱导调节性T细胞，在免疫赦免中发挥重要作用。这一发现促使我们测试使用α-MSH抑制自身免疫性疾病，并促进对自身抗原重新建立免疫耐受的可能性。为了验证这种可能性，在出现麻痹的最初迹象时，给患有实验性自身免疫性脑脊髓炎（EAE）的SJL小鼠注射α-MSH。与未治疗的EAE小鼠相比，接受α-MSH治疗的小鼠EAE的严重程度和发作速度显著降低。与产生干扰素-γ的未治疗小鼠脾细胞相比，接受α-MSH治疗的EAE小鼠的脾细胞在受到髓鞘少突胶质细胞糖蛋白（PLP）抗原刺激时会产生转化生长因子-β（TGF-β）。当对接受α-MSH治疗的EAE小鼠进行再次免疫时，第二次EAE发作延迟了一周。尽管这种延迟可能是由于α-MSH治疗诱导了产生TGF-β的脾细胞，但它不足以抑制未治疗小鼠的PLP抗原刺激的脾细胞产生干扰素-γ，也无法抑制最终的第二次EAE发作。因此，在麻痹发作时注射α-MSH在减轻EAE的严重程度和发作速度方面极其有效，随后诱导潜在的PLP特异性调节性T细胞表明，可以尝试将α-MSH疗法作为治疗方案的一部分，对中枢神经系统自身免疫性疾病进行免疫调节和免疫抑制。
