In vivo studies of articular tissue damage mediated by catabolin/interleukin 1.

Abstract

SUMMARY A partially purified porcine synovial catabolin interleukin 1 (CF) preparation was injected intra-articularly into rabbit stifle (knee) joints. Radiolabelled CF was rapidly cleared from the joint (0.4 h). Repeated injections of CF caused a marked loss of articular cartilage glycosaminoglycan (GAG) and a great increase in synovial fluid GAG. 35So4 uptake was inhibited. Time course experiments after a single injection produced similar loss of GAG from knee cartilages, which was maximal three days after injection. The above changes were significantly less with heat inactivated preparations. Loss of articular cartilage metachromasia was found histologically, and an acute synovitis occurred together with lymphocytic foci and plasma cell infiltration.Key words: glycosaminoglycan, 35S uptake, cartilage matrix degradation, synovial inflammation, ILl, catabolin.Currently the role of locally produced cytokines of the interleukin 1 (IL1) family in the pathogenesis of articular diseases is the subject of much speculation. Catabolin/ILl-like activity is both synthesised and secreted from a variety of connective tissues and cells of human and animal origin maintained in culturel-3; substantial activity has also been shown in a study of human rheumatoid synovial tissue.4 The action of porcine synovial catabolin/IL1 and porcine leucocyte ILl on cartilage and bone in organ culture has been extensively studied. The work presented below is a preliminary investigation of the action of partially purified synovial catabolin/IL1 (CF) on joint tissues when given intra-articularly. Changes in cartilage catabolism and synthetic activity were found together with inflammatory changes in the synovium. Materials and methods Old English rabbits (2-3 kg) were used throughout. Partially purified porcine synovial catabolin/ILI (CF)18 was labelled with 1311 using lodobeads (Pierce Chemical Co, Rockford, Illinois) according to Markwell.19 After the reaction of carrier sodium iodide was added to give a final concentration of 100 mg/ml, and the solution was dialysed for 72 h in two changes of deionised water and a third of physiological saline. All these procedures were performed at 4°C. The final product had an activity of 6 MBq/mg protein. The filter sterilised preparation was then injected intra-articularly into the knees of four rabbits who had been previously sedated with 'Hypnorm' (0-4 ml/kg) (Jannsen Pharmaceuticals, Beerse, Belgium). The rabbits were then positioned rapidly with their knees underneath vertical, lead 527 528 Dingle, Page Thomas, King, Bard collimated gamma scintillation probes and the radioactivity measured as previously described.20 Counting was repeated at intervals up to 24 h.In the experiment to determine in vivo catabolic action of the cytokine preparation a group of five rabbits was injected with CF and heat inactivated CF (10% of the activity of CF when tested in the organ culture bioassay) into each of their knees in a volume of 0-2 ml. The preparations were randomly allocated to the left and right knees, and...

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“…Tumour necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 are clearly involved in the arthritic process since all three cytokines are present in synovial¯uid and can be detected immunohistochemically in the in¯amed rheumatoid synovium (Delauran et al, 1992;Farahat et al, 1993). Furthermore, both local and systemic levels of each cytokine correspond to disease activity (Eastgate et al, 1988;Westacott et al, 1990;Feldmann et al, 1990), and TNF and IL-1 have profound catabolic e ects on articular cartilage explants from numerous species (Dingle et al, 1987a;Shinmei et al, 1989).…”

Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

“…On day 14, medium was removed, and the remaining cartilage was digested with papain. Active collagenase was analyzed in day 14 medium by 3 Addition of selective matrix metalloproteinase 1 inhibitors to resorbing bovine nasal cartilage. Bovine nasal cartilage discs were cultured in medium with or without IL-1␣/OSM (0.2/2 ng/ml) with or without BRL54418 or BRL56613A (0.01-100 M).…”

“…In experimental cartilage models, chondrocytes respond to proinflammatory cytokines such as interleukin-1 (IL-1), resulting in the breakdown of the ECM. Degradation of proteoglycan is rapid and reversible (2); however, the breakdown of collagen is slow and is thought to be essentially irreversible (3).…”

Elevated substance p and accelerated cartilage degradation in rabbit knees injected with interleukin‐1 and tumor necrosis factor

“…Substance P also induces secretion of IL-1 activity by P388D1 cells (17). In animal studies, the injection of IL-1 can induce inflammation and cartilage proteoglycan loss (18)(19)(20)(21)(22)(23), as well a s cause fever (24) in rabbits. Whether or not substance P is produced in vivo after IL-1 injection has not been reported.…”