The inflammatory potential of IL-2: Local induction of a specific chronic granulomatous lesion in mice

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.