Recombinant human interleukin-1 alpha and recombinant human interleukin-1 beta stimulate cartilage matrix degradation and inhibit glycosaminoglycan synthesis.
Recombinant human interleukin-1 alpha (rhIL-1 alpha) and recombinant human interleukin 1 beta (rhIL-1 beta) stimulated the time- and concentration-dependent release of glycosaminoglycan (GAG) from bovine nasal cartilage explants. Maximum GAG release occurred during six to eight days of cartilage exposure to either species of rhIL-1; and rhIL-1 alpha was consistently more potent than rhIL-1 beta. In addition to inducing cartilage matrix resorption, rhIL-1 alpha and rhIL-1 beta also inhibited the incorporation of [35SO4]sulfate into cartilage, which is a reflection of the suppression of GAG synthesis. IL-1 had no capacity to stimulate GAG relase from or inhibit GAG synthesis by dead cartilage. Cycloheximide, an inhibitor of protein synthesis, and 1, 10-phenanthroline, a metalloproteinase inhibitor, suppressed rhIL-1-stimulated cartilage matrix resorption. Polyclonal antisera to rhIL-1 alpha and rhIL-1 beta specifically neutralized the respective cytokines.
Smith
R J
RJ
Department of Hypersensitivity Diseases Research Upjohn Company, Kalamazoo, Michigan 49001.
Rohloff
N A
NA
Sam
L M
LM
Justen
J M
JM
Deibel
M R
MR
Cornette
J C
JC
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002417:Cattle; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D010618:Phenanthrolines / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011994:Recombinant Proteins; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D007375:Interleukin-1; D010618:Phenanthrolines; D011994:Recombinant Proteins; D013431:Sulfates; D003513:Cycloheximide; D011112:Polymyxin B; C025205:1,10-phenanthroline