Susceptibility to physiological concentrations of IL-1β varies in cartilage at different anatomical locations on human osteoarthritic knee joints

Objectives: To determine whether cartilage biopsies from specific regions of osteoarthritic knee joints differ in susceptibility to the degradative effects of the amounts of interleukin-1beta (IL-1beta; 1-10 pg/ml) found in osteoarthritic joints, To establish whether biopsies are sensitive to the effects of either IL-1beta or TNFalpha or both catabolic cytokines. Methods: Cartilage from specified regions of 22 osteoarthritic knee joints was examined. Biopsies were incubated for 14 days without or with IL-1beta or TNFalpha at physiological concentrations and GAG release into supernatants assessed. Results: Variation was observed in susceptibility to the effects of 1-10 pg/ml IL-1beta in biopsies from different sites within the same joints and the same site in different joints. The number of regions responding to the cytokine increased significantly (P<0.0063, Chi square test) with concentration: only 10% (2/21) of all regions tested were susceptible to the effects of 1 pg/ml IL-1β, whereas 45% (9/20) were susceptible to the effects of 5 pg/ml and 56% (10/18) to the effects of 10 pg/ml IL-1β, Significantly fewer regions (4%, 2/47) responded to both IL-1β and TNFα (P<0.047, Chi square test); biopsies from some patients responded to neither cytokine. Conclusions: IL-1beta, at the low concentrations detected in joints, can degrade cartilage from susceptible locations. Susceptibility of some cartilage biopsies to the effects of either IL-1beta and TNFalpha, but not both, suggests the signalling receptors for the two major catabolic cytokines are not usually expressed concurrently. The fact that some biopsies respond to neither cytokine suggests that in some patients the local concentration of inhibitors may be high or that other catabolic stimuli predominate. These results could have important implications for pharmacological intervention strategies. (C) 2002 OsteoArthritis Research Society International.