LONG-TERM PROTECTION AGAINST THE EFFECTS OF TUMOR-NECROSIS-FACTOR BY CONTROLLED DELIVERY OF THE SOLUBLE P55 TNF RECEPTOR

Chronic inflammatory diseases are associated with increased soluble tu mour necrosis factor (TNF) receptor concentrations in serum, To obtain such an increase, we implanted mice with ethylene vinyl-acetate or po ly (lactic-co-glycolic) acid copolymers containing human soluble p55 T NF receptor, Copolymers containing rather small amounts of the recepto r (about 20 mu g) maintained prolonged increases in serum receptor con centrations, Mice implanted with these copolymers were effectively pro tected against lethal wasting and from arthritis resulting from chroni c exposure to TNF, These findings suggest that the increased productio n of soluble TNF receptors in chronic inflammatory diseases counteract s deleterious effects of TNF, and suggest a therapeutic application fo r the natural forms of the receptors in such diseases. (C) 1996 Academ ic Press Limited