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 tumour necrosis factor (TNF) receptor concentrations in serum, To obtain such an increase, we implanted mice with ethylene vinyl-acetate or poly (lactic-co-glycolic) acid copolymers containing human soluble p55 TNF receptor, Copolymers containing rather small amounts of the receptor (about 20 mu g) maintained prolonged increases in serum receptor concentrations, Mice implanted with these copolymers were effectively protected against lethal wasting and from arthritis resulting from chronic exposure to TNF, These findings suggest that the increased production of soluble TNF receptors in chronic inflammatory diseases counteracts deleterious effects of TNF, and suggest a therapeutic application for the natural forms of the receptors in such diseases. (C) 1996 Academic Press Limited