Liu X, Linnington C, Webster H D, Lassmann S, Yao D L, Hudson L D, Wekerle H, Kreutzberg G W
Laboratory of Experimental Neuropathology, NINDS, National Institutes of Health, Bethesda, MD 20892, USA.
J Neurosci Res. 1997 Mar 1;47(5):531-8. doi: 10.1002/(sici)1097-4547(19970301)47:5<531::aid-jnr8>3.0.co;2-i.
To test the effects of insulin-like growth factor-I (IGF-I) on clinical deficits, lesion severity, and immune cell response in acute, non-demyelinative experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis rats by passive transfer of an MBP-reactive T lymphocyte line. Four days after receiving 5 x 10(5) MBPL-1 T cells intravenously, ten pairs of rats had the same mild degree of tail and hind limb weakness. Ten were given 300 micrograms IGF-I i.v. twice daily for 6 days, and the other 10 received the same volume of 0.89% NaCl. Pairs of rats were sacrificed after 4 days and 6 days of IGF-I and placebo treatment and spinal cord sections were processed for immunostaining, in situ hybridization, and morphological examination. IGF-I treatment decreased clinical deficits, lesion numbers, and lesion areas significantly. Numbers of CD4-positive T cells, alpha/beta TCR-positive cells, and ED-1-positive macrophages were also significantly reduced by IGF-I treatment. Similar reductions were found in our second trial, when 11 days of placebo and IGF-I injections began the day after transfer. No demyelination was observed in either toluidine blue-stained semithin sections or sections immunostained with an antibody raised against myelin basic protein (MBP). We conclude that IGF-I-induced reductions in immune cell responses can occur in the absence of demyelination and are of major importance in decreasing clinical deficits and lesion severity in EAE. If IGF-I has similar effects in multiple sclerosis, we think that it will be useful therapeutically.
为了测试胰岛素样生长因子-I（IGF-I）对急性非脱髓鞘性实验性自身免疫性脑脊髓炎（EAE）的临床缺陷、病变严重程度和免疫细胞反应的影响，我们通过被动转移MBP反应性T淋巴细胞系在Lewis大鼠中诱导EAE。静脉注射5×10⁵个MBPL-1 T细胞4天后，十对大鼠出现相同程度的轻度尾巴和后肢无力。十只大鼠每天静脉注射300微克IGF-I，共6天，另外十只大鼠接受相同体积的0.89%氯化钠。在IGF-I和安慰剂治疗4天和6天后处死大鼠对，并对脊髓切片进行免疫染色、原位杂交和形态学检查。IGF-I治疗显著降低了临床缺陷、病变数量和病变面积。IGF-I治疗还显著减少了CD4阳性T细胞、α/β TCR阳性细胞和ED-1阳性巨噬细胞的数量。在我们的第二项试验中也发现了类似的减少，即在转移后第二天开始进行11天的安慰剂和IGF-I注射。在甲苯胺蓝染色的半薄切片或用抗髓鞘碱性蛋白（MBP）抗体免疫染色的切片中均未观察到脱髓鞘现象。我们得出结论，IGF-I诱导的免疫细胞反应减少可在无脱髓鞘的情况下发生，并且在降低EAE的临床缺陷和病变严重程度方面具有重要意义。如果IGF-I在多发性硬化症中具有类似作用，我们认为它将具有治疗价值。
