Zuany-Amorim C, Créminon C, Nevers M C, Nahori M A, Vargaftig B B, Pretolani M
Unit of Cellular Pharmacology, Associated Unit of Pasteur Institut/INSERM Unit 285, Paris, France.
J Immunol. 1996 Jul 1;157(1):377-84.
Sensitized BALB/c mice challenged i.p. with 1 microgram of OVA showed IL-5 release in the peritoneal lavage fluid, which peaked at 6 h and decreased thereafter. This was followed by a massive eosinophil accumulation, which started at 6 h and reached a plateau between 24 and 48 h. The i.p. injection of recombinant murine (rm) IL-10 (0.01-0.1 microgram/cavity) along with OVA reduced IL-5 release at 6 h and allergic eosinophilia at 6, 24, and 48 h. rmIL-10 also blocked in vitro IL-5 generation by sensitized peritoneal cells cultured in the presence of OVA. The inhibitory effect of rmIL-10 on Ag-induced eosinophilia and IL-5 release was suppressed by pretreatment of the animals with 1 mg/mouse of a neutralizing anti-mIL-10 mAb. Flow cytometric analysis revealed an increase in the number of CD4+ and CD8+ T lymphocytes and in the number of CD25+/CD4+ cells in the peritoneal lavage fluid collected 24 and 48 h after challenge, respectively; these numbers were reduced significantly by the administration of 0.1 microgram of rmIL-10. Finally, rmIL-10 failed to modify the anti-CD3-induced IL-5 release in vivo in the peritoneal cavity and in vitro from purified spleen CD4+ T lymphocytes. This suggests that rmIL-10 acts indirectly, by deactivating APC, rather than directly on T cell activation. These findings indicate that rmIL-10 displays anti-allergic activity in sensitized BALB/c mice by preventing Ag-induced CD4+ T lymphocyte and eosinophil accumulation as well as IL-5 release in the peritoneal cavity.
用1微克卵清蛋白腹腔注射攻击致敏的BALB/c小鼠，可使腹腔灌洗液中白细胞介素-5释放，在6小时达到峰值，之后下降。随后出现大量嗜酸性粒细胞积聚，始于6小时，在24至48小时达到平台期。与卵清蛋白一起腹腔注射重组鼠白细胞介素-10（0.01 - 0.1微克/腔）可减少6小时时白细胞介素-5的释放以及6、24和48小时时的过敏性嗜酸性粒细胞增多。重组鼠白细胞介素-10还可在体外阻断卵清蛋白存在下培养的致敏腹腔细胞产生白细胞介素-5。用1毫克/只的中和抗小鼠白细胞介素-10单克隆抗体预处理动物，可抑制重组鼠白细胞介素-10对抗原诱导的嗜酸性粒细胞增多和白细胞介素-5释放的抑制作用。流式细胞术分析显示，攻击后24小时和48小时收集的腹腔灌洗液中，CD4⁺和CD8⁺T淋巴细胞数量以及CD25⁺/CD4⁺细胞数量分别增加；给予0.1微克重组鼠白细胞介素-10可使这些数量显著减少。最后，重组鼠白细胞介素-10未能改变腹腔内体内抗CD3诱导的白细胞介素-5释放以及体外纯化脾CD4⁺T淋巴细胞的白细胞介素-5释放。这表明重组鼠白细胞介素-10通过使抗原呈递细胞失活间接发挥作用，而非直接作用于T细胞活化。这些发现表明，重组鼠白细胞介素-10通过防止抗原诱导的CD4⁺T淋巴细胞和嗜酸性粒细胞积聚以及腹腔内白细胞介素-5释放，在致敏的BALB/c小鼠中表现出抗过敏活性。
