白细胞介素1受体拮抗剂对白细胞介素1α诱导的眼眶成纤维细胞表达细胞间黏附分子1及其与外周血单个核细胞黏附的抑制作用

目的 研究白细胞介素1受体拮抗剂（IL-1ra)对白细胞介素1α（IL-1α）诱导的眼眶成纤维细胞表达细胞间黏附分子1（ICAM-1）及眼眶成纤维细胞与外周血单个核细胞（PBMC）黏附的抑制作用。方法 实验组标本为取自5例Graves‘眼病（GO）患者的球后结缔组织和眼外肌标本,对照组标本取自2例外伤引起的角膜葡萄肿行眼球摘除术者和2例斜视矫正术患者术中所取眼眶结缔组织和眼外肌标本。两组标本分别应用不同浓度的IL-1α或（和）IL-1ra处理培养的眼眶成纤维细胞。应用细胞免疫组化法检测IL-1ra对IL-1α诱导的眼眶成纤维细胞表达ICAM-1的影响;应用荧光显微镜检测预先标记的PBMC与培养的眼眶成纤维细胞的黏附能力。应用抗ICAM-1单克隆抗体中和抗体检测ICAM-1在IL-1α诱导的黏附过程中的作用。结果 IL-1ra培养后,IL-1α诱导的两组眼眶成纤维细胞表达ICAM-1均减弱;且IL-1ra呈浓度和时间依赖性抑制IL-1α诱导的PBMC与眼眶成纤维细胞的黏附。抗人ICAM-1单克隆抗体呈浓度依赖性抑制PBMC与眼眶成纤维细胞的黏附。结论 IL-1ra可抑制IL-1α诱导的眼眶成纤维细胞表达ICAM-1及其与PBMC的黏附,IL-1α诱导眼眶成纤维细胞表达ICAM-1可能在促进PBMC黏附到成纤维细胞的过程中起重要作用。IL-1ra可望用于GO的治疗和预防。

The inhibition effect of interleukin-1 receptor antagonist on interleukin-1 alpha-induced intercellular adhesion molecule-1 expression on orbital fibroblasts and adhesion of peripheral blood mononuclear cells

OBJECTIVE: The aim was to identify whether interleukin-1 receptor antagonist (IL-1ra) inhibits interleukin-1 alpha (IL-1 alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured orbital fibroblasts, and adhesion of peripheral blood mononuclear cells (PBMC) to orbital fibroblasts, and to investigate the clinical application potential of IL-1ra in the treatment of Graves' ophthalmopathy (GO). METHODS: Cultured orbital fibroblasts from patients with GO and controls were challenged with IL-1 alpha or/and IL-1ra. Immunocytochemical staining was used to examine the changes of ICAM-1 in response to IL-1ra treatment; fluorescent photomicroscope was used to measure the adhesion between the labeled PBMC and orbital fibroblasts. Neutralizing antibody against ICAM-1 was used to demonstrate the role of ICAM-1 in the IL-1 alpha-induced adhesion. RESULTS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts both from GO patients and controls; IL-1ra inhibits IL-1 alpha-induced adhesion of PBMC to orbital fibroblasts in a concentration and time dependent manner. Moreover, a monoclonal anti-human ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 alpha-induced adhesion of PBMC to the fibroblasts. CONCLUSIONS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts and the adhesion of PBMC to fibroblasts. IL-1 alpha-induced ICAM-1 expression may play an important role in the adhesion process. IL-1ra may be useful in the prevention or treatment of GO.