奥曲肽对EAE豚鼠外周血单个核细胞分泌IFN-γ、IL-4水平的影响

Effect of octreotide on the release of 1FN-γ,IL-4 by peripheral blood mononuclear cells in guinea pigs with experimental allergic encephalomyelitis

目的通过研究奥曲肽对急性实验性自身免疫性脑脊髓炎（EAE）豚鼠外周血单个核细胞（PBMC）分泌γ干扰素（IFN-γ）、白细胞介素-4（IL-4）水平的影响，探讨奥曲肽对EAE发病保护作用的免疫学机制。方法将40只雌性豚鼠随机分为健康对照组、EAE对照组和EAE高、低剂量治疗组，每组各10只。EAE对照组及EAE高、低剂量治疗组采用粗制髓鞘碱性蛋白（cMBP）诱发急性EAE，EAE低、高剂量治疗组自造模前7d始分别按体质量3、12μg／（kg·d）予皮下注射奥曲肽直至试验结束。观察4组豚鼠神经功能障碍评分变化，并用ELISA法测定PBMC培养上清液中IFN-γ和IL-4水平变化。结果EAE高、低剂量治疗组神经功能障碍评分较EAE对照组显著降低（P〈0．01，P〈0．05），且EAE高剂量治疗组降低更明显（P〈0．05）。PBMC分泌IFN-γ水平EAE低、高剂量治疗组、EAE对照组较健康对照组显著升高（P〈0．01），EAE高、低剂量治疗组较EAE对照组显著降低（均P〈0．01），且EAE高剂量治疗组降低更明显（P〈0．05）。PBMC分泌IL-4水平EAE对照组较健康对照组明显降低（P〈0．01），EAE高、低剂量较EAE对照组均明显增高（均P〈0．01），且EAE高剂量治疗组增高更明显（P〈0．05）。EAE对照组及EAE高、低剂量治疗组发病高峰期外周血IFN-γ／IL-4比值与神经功能障碍评分均呈正相关（r=0．753、P〈0．05，r=0．835、P〈0．01，r=0．779、P〈0．01）。结论奥曲肽对EAE豚鼠发病具有保护作用，其作用机制可能是通过抑制IFN-γ生成、促进IL-4生成而发挥对Th1／Th2失衡的调节作用。

Objective To investigate the immunological mechanism underlying octreotide against experimental allergic encephalomyelitis （EAE） by studying the effect of octreotide on the release of IFN-γ, IL-4 from peripheral blood mononuclear cells （PBMC） of guinea pigs suffering from EAE. Methods Forty female guinea pigs were divided randomly into the normal control group, the EAE control group, the low dose treating EAE group and the high dose treating EAE group, 10 guinea pigs in each group respectively. Acute EAE was induced by crude myelin basic protein （cMBP） in the related animals. Seven days before the experiments, animals in the low-dose treating EAE group were subcutaneously injected with octreotide 3 μg/kg, the high dose treating EAE group with octreotide 12 μg/kg until the end of the experiment. The levels of neurological disorder changes were recorded and changes of IFN-γ and IL-4 in culture supernatant were tested by ELISA method： Results The levels of neurological disorder in the high dose treated EAE group and the low close treated EAE group were lower than that of the EAE control group （P〈0.01, P〈0.05）, the high dose treated EAE group was the lowest （P〈0. 05）. The release of IFN-γ from PBMC in the EAE control group was significantly higher than that in the normal control group （P〈0.01）, and significantly higher than that in the low dose treated EAE group and the high dose treated EAE group （All P〈0.01）, the high dose treated EAE group was the lowest （P〈0.05）. The release of IL-4 from PBMC in the EAE control group was significantly lower than that in the normal control group （P〈0.01）, and significantly lower than that in the low dose treated EAE group and the high dose treated EAE group （All P〈0.01）, the high dose treated EAE group was the highest （P〈0. 05）. In fastigium of EAE in the EAE control group, the low close treated EAE group and the high dose treated EAE group, the ratio of IFN-γ and IL-4 was proportional to the level of neurological disorder （r=0. 753, P〈0.05; r=0. 835, P〈0.01; r=0. 779, P〈0. 01）. Conclusions Octreotide had protective effect over guinea pigs with EAE. It restrained Thl type eytokine IFN-γ and promoted Th2 type cytokine IL-4. The mechanism may be produced by inhibiting IFN-γ, enhancing IL-4 generation.