Antibody to interleukin 1 inhibits the cartilage degradative and thymocyte proliferative actions of rheumatoid synovial culture medium.
Cartilage breakdown in rheumatoid arthritis results from (a) lytic action by synovial enzymes, and (b) release of synovial catabolin, now believed to be a form of interleukin 1 (IL-1), causing chondrocytes to degrade their matrix. Rheumatoid synovial culture media were tested for their ability to stimulate cartilage degradation (proteoglycan release from bovine nasal cartilage discs) and thymocyte proliferation (3H-thymidine incorporation) in the absence or presence of anti-IL-1. Degradation of living cartilage, stimulated 2-fold by synovial culture media, was inhibited up to 80% by anti-IL-1. Residual breakdown in living cartilage and synovial culture media induced breakdown in dead cultures were of similar magnitude, and both were unaffected by antibody treatment. Proteoglycan products released from synovial culture media treated cartilage were of smaller average molecular weight (Sepharose CL-2B), and such size reduction was inhibited by anti-IL-1 treatment. Synovial culture media that stimulated cartilage degradation also stimulated thymocyte proliferation; the latter was fully suppressible by anti-IL-1. One of 8 synovial culture media contained an inhibitor(s) of thymocyte proliferation, removable by dialysis. We conclude (1) rheumatoid synovial catabolin activity is due to a form of IL-1. (2) A minor nonsuppressible component of synovial culture media stimulated breakdown, identical in living and killed cartilage, is due to passive transfer of enzymic activity. (3) Cultured rheumatoid synovium releases both IL-1 and an inhibitor(s) of IL-1 action.
Yodlowski
M L
ML
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Hubbard
J R
JR
Kispert
J
J
Keller
K
K
Sledge
C B
CB
Steinberg
J J
JJ
D000906:Antibodies / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D053583:Interleukin-1beta; D011509:Proteoglycans / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology*; D014316:Tritium
D000906:Antibodies; D003470:Culture Media; D007375:Interleukin-1; D053583:Interleukin-1beta; D011509:Proteoglycans; D014316:Tritium; D013936:Thymidine