Synergism of basic fibroblast growth factor and interleukin-1 beta to induce articular cartilage-degradation in the rabbit.
Interleukin-1 beta (IL-1) and basic fibroblast growth factor (bFGF) synergistically induce proteases in vitro. To investigate this synergy in vivo, we injected IL-1 and bFGF alone and in combination into the lapine knee. Three days later, we compared the glycosaminoglcan (GAG) content of tibial cartilage of cytokine-treated and contralateral control-knees. IL-1 caused significant increases of granulocytes and GAG in the synovial fluid but minor cartilage-GAG losses of 11, 11 & 16% at 5kU, 10 kU and 100 kU IL-1/knee, respectively. bFGF at 2 and 10 micrograms/knee caused no changes. 10 micrograms bFGF in combination with 10 kU IL-1 induced a 33% GAG loss (p less than 0.01) that lasted 21 days. IL-1/bFGF induced cartilage degradation may be useful to 1) evaluate agents which modulated proteoglycan catabolism and 2) assess factors that accelerate cartilage-repair.
Stevens
P
P
Department of Pharmacology, Amgen, Thousand Oaks, CA 91320.
Shatzen
E M
EM
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects; D006614:Hindlimb; D007375:Interleukin-1 / Q000494:pharmacology*; D007592:Joint Diseases / Q000139:chemically induced* / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2