Long-term protection against the effects of tumour 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 micrograms) 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.
Eliaz
R
R
Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Wallach
D
D
Kost
J
J
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001168:Arthritis / Q000517:prevention & control; D001672:Biocompatible Materials; D002100:Cachexia / Q000517:prevention & control; D003692:Delayed-Action Preparations; D006801:Humans; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011145:Polyvinyls; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects*
D015703:Antigens, CD; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D011145:Polyvinyls; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016438:ethylenevinylacetate copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid