Matsushima S, Yoshitoshi T, Mahalak S M, Shichi H
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI 48201.
Jpn J Ophthalmol. 1990;34(3):306-13.
Investigations were carried out on the immunosuppressive effect of gramicidin S (GrS), a cyclic peptide antibiotic produced by Bacillus brevis, on the onset of experimental ocular neuritis and allergic encephalomyelitis in Lewis rats immunized with rat brain homogenates. The criteria for evaluation of the drug effect were changes in body weight, activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), clinical manifestations such as paralysis of lower extremities and histopathological changes. Clinical symptoms and body weight reduction were effectively prevented by GrS treatment of immunized animals. The activity of the myelin marker enzyme CNPase was markedly decreased in the lumbar spinal cord of encephalitogen-immunized animals on day 16 (ie 16 days after immunization) and the decrease of enzymatic activity was partially prevented by GrS administration. On the other hand, the CNPase activity of the retrobulbar optic nerve of inoculated animals remained essentially the same as that of healthy control animals, although inflammatory changes were prominent in the optic nerve. Histopathological changes observed in the optic nerve and spinal cord of diseased animals were virtually absent in GrS-treated animals. A possible mechanism of the immunosuppressive activity of GrS is discussed.
对短芽孢杆菌产生的环肽抗生素短杆菌肽S(GrS)对用大鼠脑匀浆免疫的Lewis大鼠实验性视神经炎和过敏性脑脊髓炎发病的免疫抑制作用进行了研究。评估药物效果的标准包括体重变化、2',3'-环核苷酸3'-磷酸水解酶(CNPase)活性、诸如下肢麻痹等临床表现以及组织病理学变化。通过对免疫动物进行GrS治疗,有效地预防了临床症状和体重减轻。在免疫原免疫动物的腰脊髓中,髓鞘标记酶CNPase的活性在第16天(即免疫后16天)显著降低,而通过给予GrS部分预防了酶活性的降低。另一方面,接种动物的球后视神经的CNPase活性与健康对照动物基本相同,尽管视神经中的炎症变化很明显。在患病动物的视神经和脊髓中观察到的组织病理学变化在GrS治疗的动物中几乎不存在。讨论了GrS免疫抑制活性的可能机制。