Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States.
J Neuroimmunol. 2011 Mar;232(1-2):131-5. doi: 10.1016/j.jneuroim.2010.10.030. Epub 2010 Nov 16.
Ingested type I IFN and SIRS peptide inhibit EAE. We examined whether another immunoactive protein, ACTH, would have similar anti-inflammatory effects in EAE after oral administration. B6 mice were immunized and gavaged with control saline or ACTH starting on the onset of disease. ACTH decreased clinical score and decreased inflammatory foci. CNS lymphocytes showed decreases in IL-17 (T(eff)) and Th1-like encephalitogenic cytokines IL-2 and IFN-γ in the ACTH fed group compared to the mock fed group. Adoptive transfer of ACTH fed splenocytes into MOG immunized recipient mice with early clinical disease suppressed disease severity compared to splenocytes from mock fed donors. The protected recipients showed decreased splenic IL-17 (T(eff)) and Th1-like cytokine IFN-γ and increased CNS secretion of immunoregulatory IL-4 and chemokine M-CSF. Splenic CD4+CD25+ FoxP3+ frequency doubled in ACTH fed compared to control fed mice. Increased immuno-regulatory IL-4 and M-CSF secreting cell populations is the mechanism of protection in adoptively protected recipients and reflects the direct action of ACTH on the immune system.
摄入型 I 型 IFN 和 SIRS 肽抑制 EAE。我们研究了另一种免疫活性蛋白，即 ACTH，在口服后是否对 EAE 具有类似的抗炎作用。从疾病发作开始，用对照生理盐水或 ACTH 灌胃 B6 小鼠进行免疫。ACTH 降低了临床评分并减少了炎症灶。与模拟喂养组相比，ACTH 喂养组的 CNS 淋巴细胞中白细胞介素 17（T(eff)）和 Th1 样致脑炎细胞因子白细胞介素 2 和干扰素-γ减少。与来自模拟喂养供体的脾细胞相比，将 ACTH 喂养的脾细胞过继转移到有早期临床疾病的 MOG 免疫受体小鼠中可抑制疾病严重程度。受保护的受体显示出脾细胞中白细胞介素 17（T(eff)）和 Th1 样细胞因子干扰素-γ减少，以及中枢神经系统中免疫调节白细胞介素 4 和趋化因子 M-CSF 的分泌增加。与对照喂养组相比，ACTH 喂养组的脾细胞中 CD4+CD25+FoxP3+频率增加了一倍。增加的免疫调节 IL-4 和 M-CSF 分泌细胞群是在过继保护受体中保护的机制，反映了 ACTH 对免疫系统的直接作用。
