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

• Published in: Journal of leukocyte biology Vol. 60; no. 1; pp. 27 - 36
• Main Authors: Dunn, Colin J., Hardee, Marilyn M., Fidler, Stephen F., Shields, Sharon K., Chosay, John G.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-07-1996
• Subjects: adhesion molecule expression; Animals; Antigens, Differentiation, Myelomonocytic - analysis; Antigens, Differentiation, Myelomonocytic - biosynthesis; Cattle; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - biosynthesis; chronic inflammation; cytokines; Eosinophils - drug effects; Eosinophils - pathology; Eosinophils - physiology; Female; Granulocytes - drug effects; Granulocytes - pathology; Granulocytes - physiology; Granulomatous Disease, Chronic - chemically induced; Granulomatous Disease, Chronic - pathology; Granulomatous Disease, Chronic - physiopathology; Humans; Inflammation; Intercellular Adhesion Molecule-1 - analysis; Intercellular Adhesion Molecule-1 - biosynthesis; Interleukin-2 - toxicity; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - pathology; Leukocytes, Mononuclear - physiology; lymphocytes; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; neovascularization; Platelet Endothelial Cell Adhesion Molecule-1; Recombinant Proteins - toxicity; Reference Values; Serum Albumin, Bovine; slow‐release interleukin‐2; Vascular Cell Adhesion Molecule-1 - analysis; Vascular Cell Adhesion Molecule-1 - biosynthesis
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.60.1.27

Subcutaneous injection of recombinant human interleukin‐2 (rhuIL‐2) at 102‐104 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 (102–104 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.