Synthesis of arachidonate oxidation products by synovial joint tissues during the development of chronic erosive arthritis

Abstract

An animal model, antigen-induced arthritis in the rabbit, was used to investigate the synthesis of arachidonic acid oxidation products (eicosanoids) by tissues of the knee joints during the initiation and early phase of this developing chronic destructive lesion. High concentrations of immunoreactive prostaglandin E₂ and immunoreactive leukotriene B₄ were found to be present in the synovial fluid in the early lesion. These levels rapidly declined, as did the ablity of the infiltrating cells of the arthritic joint fluids to synthesize leukotriene B₄. Articular cartilage and synovial lining were maintained for 24 hours in nonproliferative organ culture, and the synthesis of eicosanoids was measured by assay of the culture fluids. The synovial lining was the major source of eicosanoids. Synthesis of prostaglandin E₂, prostacyclin, thromboxane A₂, and leukotriene B₄ by the arthritic synovial lining was low during the first few days, but reached maximal values between day 5 and day 15 of disease duration. Maximal eicosanoid production occurred around the time that damage to articular cartilage and bone has been reported to occur, though it is not certain that these two events are linked. It was demonstrated that, in chronic lesions, the arthritic synovial lining was still producing elevated levels of eicosanoids compared with levels in the control tissue.