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Additional info for Annual Review of Immunology Volume 16 1998

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Rev. Immunol. 16:27-55. org by HINARI on 08/31/07. For personal use only. IL-1 RECEPTOR ANTAGONIST 45 knee (157). IL-1Ra protein was produced in the knees of autografted animals through five weeks and was biologically active, as determined by inhibition of IL-1-induced neutrophil infiltration, synovial thickening, and degradation of cartilage proteoglycans (157, 158). Furthermore, the recurrence of bacterial cell wall–induced arthritis in rats (159), the severity of antigen-induced arthritis in rabbits (160), and the development of collagen-induced arthritis in mice (161) all were suppressed by the delivery of IL-1Ra into the joints through the ex vivo gene therapy approach.

Thus, all three species of IL-1Ra described in the human appeared to be present in the mouse and rabbit as well: 17-kDa sIL-1Ra (present extracellularly in the human and rabbit as 22–25-kDa variably glycosylated molecules), icIL-1Ra (the 18-kDa intracellular form transcribed from an alternate mRNA), and the 16-kDa intracellular form. Production of IL-1Ra The induction of IL-1Ra production in different cells is summarized in earlier reviews (1–7). Agents and materials that have been described, in studies published through mid-1997, as stimulating IL-1Ra production in human monocytes and macrophages are summarized in Table 1.

Table 2 Animal models of disease treated with recombinant IL-1Ra Collagen-induced arthritis in mice Streptococcal cell wall–induced arthritis in rats Immune complex–induced arthritis in mice Antigen-induced arthritis in rabbits Staphylococcal-induced arthritis in rabbits Osteoarthritis in dogs Septic shock in rabbits, baboons, rats and mice Bacterial meningitis in rabbits Ischemic brain injury in rats Experimental allergic encephalomyelitis in rats Streptococcal cell wall–induced colitis in rats Experimental shigellosis in rabbits Immune complex–induced colitis in rabbits Acetic acid–induced colitis in rats Lipopolysaccharide-induced pleurisy in rabbits Monocrotaline-induced pulmonary hypertension in rats Allergen-induced late asthmatic reaction in guinea pigs Antigen-induced airway hyperreactivity in guinea pigs Bleomycin- or silica-induced pulmonary fibrosis in mice Immune complex–induced lung injury in rats Ischemia/reperfusion lung injury in rats Crescentic glomerulonephritis in rats Anti-glomerular basement membrane antibody–induced glomerulonephritis in rats Pre-term delivery in mice induced by IL-1 Osteoclast formation and bone resorption in ovariectomized mice and rats Hepatic fibrosis induced by dimethylnitrosamine in rats Post-cardiac transplant coronary arteriopathy in piglets Graft-versus-host disease in mice Streptozotocin-induced diabetes in mice more avidly to the type I IL-1 receptor but less avidly to the type II receptor was a more potent antagonist of IL-1 effects in vivo (154).

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