Dunn C J, Hardee M M, Fidler S F, Shields S K, Chosay J G
Department of Cell Biology and Inflammation Research, Upjohn Laboratories, Kalamazoo, Michigan 49007, USA.
J Leukoc Biol. 1996 Jul;60(1):27-36. doi: 10.1002/jlb.60.1.27.
Subcutaneous injection of recombinant human interleukin-2 (rhuIL-2) at 10(2)-10(4) U/mouse induced delayed (48 h) accumulation of mononuclear leukocytes with diffuse granulocytes, including eosinophils. Subcutaneous local infusion of rhuIL-2 or recombinant murine IL-2 (10(2)-10(4) U/mouse) via implanted Alzet miniosmotic pumps in mice induced chronic inflammatory lesions characterized by infiltration of large vacuolated mononuclear leukocytes, lymphoid cells, and eosinophil foci; neovascularization, with high endothelial-like cells, was prominent, exhibiting intravascular trapping and migration of large mononuclear leukocytes. Leukocyte infiltrates comprised T lymphocytes (CD4+; CD8+), B lymphocytes, and macrophages. Control infusions of bovine serum albumin (BSA) induced weak fibrotic lesions with sparse macrophage infiltration and minimal accumulation of lymphocytes; VLA4+ and ICAM-1+ leukocyte infiltrates were significantly greater in IL-2-induced lesions compared with BSA-induced lesions. Quantitative image analysis showed significantly increased lesion size in the IL-2-induced lesions compared with those induced by BSA infusion. The vascularity of IL-2-induced lesions assessed by immunostaining for platelet-endothelial cell adhesion molecule was increased compared with control, BSA-induced lesions mainly due to neovascularization. ICAM-1 and VCAM-1 expression was significantly enhanced in IL-2 lesions. No systemic pathological changes were observed following IL-2 infusion. We conclude that local slow-release of IL-2 causes the evolution and maintenance of a specific chronic inflammatory lesion.
以10²-10⁴U/小鼠的剂量皮下注射重组人白细胞介素-2（rhuIL-2）可诱导单核白细胞出现延迟（48小时）性蓄积，并伴有包括嗜酸性粒细胞在内的弥漫性粒细胞。通过植入的Alzet微量渗透泵在小鼠体内皮下局部输注rhuIL-2或重组鼠白细胞介素-2（10²-10⁴U/小鼠）可诱导慢性炎症病变，其特征为大的空泡状单核白细胞、淋巴细胞和嗜酸性粒细胞灶浸润；以高内皮样细胞为主的新生血管形成显著，表现为大单核白细胞的血管内捕获和迁移。白细胞浸润包括T淋巴细胞（CD4⁺；CD8⁺）、B淋巴细胞和巨噬细胞。牛血清白蛋白（BSA）对照输注诱导出伴有稀疏巨噬细胞浸润和极少淋巴细胞蓄积的轻度纤维化病变；与BSA诱导的病变相比，IL-2诱导的病变中VLA4⁺和ICAM-1⁺白细胞浸润显著增多。定量图像分析显示，与BSA输注诱导的病变相比，IL-2诱导的病变大小显著增加。通过血小板内皮细胞黏附分子免疫染色评估，IL-2诱导的病变血管生成较对照、BSA诱导的病变有所增加，主要是由于新生血管形成。IL-2病变中ICAM-1和VCAM-1表达显著增强。IL-2输注后未观察到全身病理变化。我们得出结论，IL-2的局部缓释导致特定慢性炎症病变的演变和维持。
