Effect of interleukin-1-beta and tumor necrosis factor-alpha on cartilage proteoglycan metabolism in vitro.
The activities of recombinant interleukin-1-beta (IL-1) and recombinant tumor necrosis factor-alpha (TNF) on cartilage proteoglycan metabolism were compared in an organ culture system. IL-1, 1 to 100 ng/ml, and TNF, 10 to 1,000 ng/ml, increased proteoglycan degradation. The concentration-response curves were parallel. The timecourse for degradation was similar for the two cytokines during a 6 day incubation. Both cytokines inhibited the synthesis of new proteoglycan as measured by 35S incorporation. The inhibition curves were parallel and concentration-related between 1 and 10 ng/ml for IL-1 and between 10 and 100 ng/ml for TNF. Maximal inhibition was 60% in the presence of IL-1 (10 ng/ml) or TNF (100 ng/ml), and plateaued at higher concentrations. IL-1 was ten fold more potent than TNF in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesis. Degradation in response to TNF, but not to IL-1, could be blocked by a polyclonal antibody to TNF. A polyclonal antibody to IL-1 could block proteoglycan breakdown in response to both cytokines suggesting that TNF may be mediating proteoglycan degradation by inducing the production of interleukin-1.
Pratta
M A
MA
E. I. Du Pont de Nemours & Co., Medical Products Department, Wilmington, DE 19880-0440.
Di Meo
T M
TM
Ruhl
D M
DM
Arner
E C
EC
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha