Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation.
Murine recombinant interleukin 1 was injected intra-articularly into mice. It induced a clear effect on patellar cartilage within 24 hours. A low dose of interleukin 1 (1 ng) elicited a significant reduction in [35S]sulphate incorporation (50%) into proteoglycans and an accelerated breakdown (twofold) of 35S prelabelled proteoglycan. Proteoglycan breakdown returned to normal rates (approximately 10%/day) 48 hours after a single interleukin 1 injection. Recovery of proteoglycan synthesis was delayed by up to 72 hours, however, which implies that repair of the depleted cartilage matrix is retarded. Interleukin 1 induced only minor joint inflammation, too slight to be held responsible for the strong suppression of proteoglycan synthesis. Vehement joint inflammation was found after repeated interleukin 1 injections. The plasma extravasation and massive infiltration and exudation of leucocytes, predominantly polymorphonuclear leucocytes, were not a mere summation of single interleukin 1 effects, but point to interleukin 1 induced local hypersensitivity. The cartilage matrices of patella and femur were heavily depleted. Measurement of the extent of loss of 35S prelabelled proteoglycan and the prolonged inhibition of [35S]sulphate incorporation indicate that both inhibition of proteoglycan synthesis and enhanced loss of proteoglycan contributed substantially to this depletion.
van de Loo
A A
AA
Department of Rheumatology, University Hospital St Radboud, Nijmegen, The Netherlands.
van den Berg
W B
WB
D000818:Animals; D001168:Arthritis / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects*
D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins