Gharaee-Kermani M, McGarry B, Lukacs N, Huffnagle G, Egan R W, Phan S H
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
J Leukoc Biol. 1998 Nov;64(5):657-66. doi: 10.1002/jlb.64.5.657.
Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukin-5 (IL-5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung IL-5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of IL-5 in pulmonary fibrosis, the effects of anti-IL-5 antibody were investigated in a model of bleomycin-induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either anti-IL-5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is IL-5. Furthermore, anti-IL-5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for IL-5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophil-dependent fibrogenic cytokine production.
已知嗜酸性粒细胞可表达能够促进纤维化的细胞因子。白细胞介素-5（IL-5）在调节嗜酸性粒细胞生成、嗜酸性粒细胞募集和活化方面起着重要作用。在肺纤维化中，肺部IL-5表达升高，其中嗜酸性粒细胞是促纤维化细胞因子的主要来源。为了确定IL-5在肺纤维化中的作用，在博来霉素诱导的肺纤维化模型中研究了抗IL-5抗体的作用。通过气管内给予博来霉素处理诱导小鼠发生纤维化。动物还接受抗IL-5抗体或对照IgG治疗。然后分析肺组织的纤维化、嗜酸性粒细胞浸润、趋化活性和细胞因子表达情况。结果表明，在嗜酸性粒细胞募集高峰期的主要趋化活性物质是IL-5。此外，抗IL-5抗体可显著降低肺组织中的嗜酸性粒细胞增多、细胞因子表达和纤维化程度。综合这些发现表明，IL-5通过调节嗜酸性粒细胞炎症以及由此产生的嗜酸性粒细胞依赖性促纤维化细胞因子，在肺纤维化中发挥重要作用。
