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.
Dunn
C J
CJ
Department of Cell Biology and Inflammation Research, Upjohn Laboratories, Kalamazoo, Michigan 49007, USA.
Hardee
M M
MM
Fidler
S F
SF
Shields
S K
SK
Chosay
J G
JG
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000096:biosynthesis; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis*; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006105:Granulomatous Disease, Chronic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D007376:Interleukin-2 / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins / Q000633:toxicity; D012016:Reference Values; D012710:Serum Albumin, Bovine; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D012710:Serum Albumin, Bovine