Effect of interleukin 1 and leukaemia inhibitory factor on chondrocyte metabolism in articular cartilage from normal and interleukin-6-deficient mice: Role of nitric oxide and IL-6 in the suppression of proteoglycan synthesis

We studied the role of IL-6 and nitric oxide (NO) in IL-1 and leukaemia inhibitory factor (LIF) induced suppression of proteoglycan synthesis, Cartilage explants of patellae and femoral heads were incubated with IL-1 or LIF, Conditioned media were analysed for IL-6 activity (B9-assay) and NO content (Griess), Proteoglycan synthesis was assessed using [S-35]sulfate incorporation. IL-1 dose dependently induced IL-6 synthesis and neutralizing IL-6 with antibodies did not reduce proteoglycan synthesis suppression, neither in explants nor in isolated chondrocytes, IL-6 independence was confirmed using cartilage from IL-6 deficient mice, IL-1 significantly increased NO release in normal and IL-6 deficient chondrocytes and addition of the NO synthase inhibitor, N-G-monomethyl-L-arginine markedly alleviated proteoglycan synthesis suppression, LIF also induced proteoglycan synthesis suppression in cartilage from normal and IL-6 deficient mice, but the suppression was neither accompanied by nor dependent on NO release, Furthermore, proteoglycan synthesis suppression during experimental arthritis was similar in both normal and IL-6 deficient mice, We concluded that IL-6 is not a necessary cofactor in IL-1 and LIF induced suppression of proteoglycan synthesis, Furthermore, only the IL-1 induced suppression was mediated by NO, suggesting that inhibition of proteoglycan synthesis may occur through different pathways. (C) 1997 Academic Press Limited.