Effect of purified human interleukin-1 on cartilage degradation.
The effects of highly purified human monocyte-derived interleukin-1 (IL-1) on bovine nasal cartilage breakdown were investigated. Cartilage degradation was determined by quantifying the fraction of total proteoglycan released from cartilage during 8 days of culture. The response appeared to be chondrocyte-dependent, for IL-1 stimulated proteoglycan (PG) release from living but not from dead (frozen-thawed) cartilage. IL-1 action on living cartilage was heat labile and concentration dependent, with significant effect at 5 U/ml and maximal effect at 10-20 U/ml. Kinetic studies showed significant stimulation of PG release by 3 days of incubation with 10 U/ml IL-1. Studies in which IL-1 was removed on day 1 or day 4 showed that the cartilage-degrading effect of this monokine was reversible. Although IL-1 caused little change in the Sepharose CL-2B chromatographic profile of released PGs using an associative elution buffer, a significant shift to lower mol wt was observed under dissociative conditions. To probe the mechanism of IL-1 action, cartilage samples were incubated with IL-1 in the presence of the protein synthesis inhibitor, cycloheximide, or the lysosomal membrane-stabilizing steroid, hydrocortisone. Cycloheximide at 5-10 micrograms/ml completely blocked IL-1-induced breakdown. One the other hand, 3 x 10(-7) M hydrocortisone had little or no effect on IL-1 action. IL-1 was also shown to stimulate the degradation of human articular cartilage.
Hubbard
J R
JR
Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Steinberg
J J
JJ
Bednar
M S
MS
Sledge
C B
CB
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D009666:Nose; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
D007375:Interleukin-1; D011509:Proteoglycans; D003513:Cycloheximide; D006854:Hydrocortisone