Induction of articular cartilage degradation by recombinant interleukin 1 alpha and 1 beta.
The purpose of this study was to compare the effects of human recombinant interleukin 1, alpha and beta, on articular cartilage. The effects of rIL-1 alpha and rIL-1 beta on proteoglycan degradation and synthesis following treatment of bovine articular cartilage in serum-free organ culture were quantified. Purified human IL-1 and both rIL-1 alpha and rIL-1 beta induced a two-fold or greater increase in glycosaminoglycan (GAG) release from cultured articular cartilage. Levels or rIL-1 alpha as low as 15 pM induced increased proteoglycan degradation whereas identical levels of rIL-1 beta did not. Killing of the cartilage cells abolished induced GAG release by all forms of IL-1. Analysis of proteoglycan size following IL-1 treatment showed limited degradation of material released into the culture medium or remaining within cartilage. Both forms of recombinant IL-1 inhibited GAG synthesis when continually present in the culture medium. Actinomycin D and cycloheximide inhibited IL-1 dependent cartilage destruction whereas indomethacin did not.
Smith
R L
RL
Division of Orthopedic Surgery, Stanford University Medical Center, California 94305.
Allison
A C
AC
Schurman
D J
DJ
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002850:Chromatography, Gel; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010206:Papain / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D003609:Dactinomycin; D003513:Cycloheximide; D010206:Papain; D007213:Indomethacin