Arthritogenic actions of recombinant IL-1 and tumour necrosis factor alpha in the rabbit: evidence for synergistic interactions between cytokines in vivo.
Intra-articular injection of highly purified or recombinant interleukin 1 (IL-1) into the rabbit knee induces a transient synovitis with leucocytic infiltration into the synovial lining and joint cavity and loss of proteoglycan from articular cartilage. Tumour necrosis factor alpha (TNF-alpha), which has many of the actions of IL-1, in the dose range 50-5,000 ng induced infiltration of leucocytes into the joint but failed to cause significant proteoglycan loss from cartilage. The nature of the leucocytic infiltrate induced by intra-articular TNF-alpha was predominantly monocytic compared with the mixed polymorphonuclear (PMN)/monocytic infiltrate induced by IL-1. Neither cytokine induced the accumulation of significant numbers of lymphocytes. In addition, on a molar basis, TNF-alpha was significantly less active than IL-1 in causing cell accumulation in the joint. Injection of submaximal doses of IL-1 and TNF into the rabbit resulted in a marked synergy with respect to the accumulation of PMN. The conclusion from these studies is that TNF-alpha could contribute to the PMN accumulation in the human joint in rheumatoid arthritis but is unlikely to be important in the destruction of articular cartilage.
Henderson
B
B
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, UK.
Pettipher
E R
ER
D000818:Animals; D001168:Arthritis / Q000209:etiology*; D002465:Cell Movement; D015232:Dinoprostone / Q000096:biosynthesis; D004357:Drug Synergism; D005347:Fibroblasts / Q000378:metabolism; D007375:Interleukin-1 / Q000009:adverse effects*; D007719:Knee Joint / Q000473:pathology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity; D013583:Synovial Membrane / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone