Division of Endocrinology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21287, USA.
Endocrinology. 2011 Oct;152(10):3803-10. doi: 10.1210/en.2011-1317. Epub 2011 Aug 16.
GH has been suggested to influence the function of the immune system in several species. Experimental autoimmune encephalomyelitis (EAE) (an animal model for multiple sclerosis) has been reported not to occur in GH-deficient (GHD) mice. The aim of this study was to elucidate the effects of GH and GHRH replacement on development of EAE in a mouse model of isolated GHD due to removal of the GHRH gene [GHRH knockout (GHRHKO)]. We studied two groups of adult female mice: 12 GH-sufficient animals (control) and 36 GHRHKO animals. All mice were immunized with myelin oligodendrocyte glycoprotein peptide, a peptide known to induce EAE. GHRHKO mice were left untreated or were treated for 4 wk with daily sc injections of recombinant GH or of a GHRH super agonist JI-38 (JI38-GHD). Evaluation of EAE symptoms was carried out daily, and T-proliferative assay and histopathological analysis of the spinal cord were performed. GHRHKO mice were less prone to develop EAE when compared with control mice. GH (but not JI-38) restored the original susceptibility of mice to the disease, despite lack of complete serum IGF-I normalization. GH treatment was also associated with a markedly increase in spleen size and T-cell proliferation specific to myelin oligodendrocyte glycoprotein peptide. GH (but not GHRH) plays an important role in the development of EAE.
生长激素（GH）被认为会影响多种物种的免疫系统功能。据报道，实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的动物模型）不会发生在生长激素缺乏症（GHD）小鼠中。本研究旨在阐明 GH 和 GHRH 替代物对由于去除 GHRH 基因（GHRHKO）而导致的孤立性 GHD 小鼠模型中 EAE 发展的影响。我们研究了两组成年雌性小鼠：12 只生长激素充足的动物（对照组）和 36 只 GHRHKO 动物。所有小鼠均用髓鞘少突胶质细胞糖蛋白肽免疫，该肽已知可诱导 EAE。GHRHKO 小鼠未接受治疗或接受每日 sc 注射重组 GH 或 GHRH 超激动剂 JI-38（JI38-GHD）治疗 4 周。每天进行 EAE 症状评估，并进行脊髓 T 细胞增殖测定和组织病理学分析。与对照组小鼠相比，GHRHKO 小鼠更不容易发生 EAE。尽管缺乏完全的血清 IGF-I 正常化，但 GH（而非 JI38）恢复了小鼠对疾病的原始易感性。GH 治疗还与脾肿大和针对髓鞘少突胶质细胞糖蛋白肽的 T 细胞增殖明显增加有关。GH（而非 GHRH）在 EAE 的发展中起着重要作用。
