['To determine the level of leukotriene B4 (LTB4) synthesized and released by synovium of patients with osteoarthritis (OA), and to study the role of lipoxygenase (LO)/cyclooxygenase (COX) products on proinflammatory cytokine and interstitial collagenase (MMP-1) synthesis.', 'Human OA synovial explants were cultured in the presence of lipopolysaccharide (L) and the ionophores ionomycin (I) and thapsigargin (T) (LIT) for 72 h at 37 degrees C, and LTB4 released into the culture medium was measured in the absence or presence of a COX-2-specific inhibitor, NS-398, or the 5-LO activating protein inhibitor Bay-x-1005. Increasing concentrations of LTB4 (10(-9) to 10(-6) M) were incubated with explants for 24 h at 37 degrees C, and interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the conditioned medium were quantitated by ELISA. The effect of endogenous eicosanoids on basal and induced levels of IL-1beta, TNF-alpha, and MMP-1 synthesis was examined by incubating explants in the presence of NS-398 and Bay-x-1005. The effect of antiinflammatory cytokines rhIL-4, IL-10, and IL-13 on basal and LTB4 dependent stimulation of IL-1beta/TNF-alpha synthesis was studied under titration conditions.', 'Physiologically relevant concentrations (10(-10) to 10(-9) mol/l) of LTB4 were produced in the presence of LIT. Bay-x-1005 abrogated LTB4 release, while NS-398 was without effect. LTB4 stimulated IL-1beta and TNF-alpha synthesis with an EC50 of 190 +/- 35 and 45 +/- 9 nmol/l, respectively. Significant concentrations of IL-1beta and TNF-alpha were released (100-200 and 500-600 pg/ml, respectively). Basal and LIT induced IL-1beta and TNF-alpha production were inhibited by Bay-x-1005 in a dose dependent manner, while the addition of NS-398 caused a potent stimulatory effect. The preferential COX-2 inhibitor also induced MMP-1 synthesis in a manner essentially identical to the proinflammatory cytokines. The antiinflammatory cytokine IL-4 blocked LTB4 dependent stimulation of IL-1beta and TNF-alpha synthesis. In contrast, IL-10 markedly stimulated both cytokines when incubated alone or in the presence of LTB4 where the effect was additive.'] Is synthesis of interleukin 1beta , tumor necrosis factor-alpha , and interstitial collagenase ( MMP-1 ) eicosanoid dependent in human osteoarthritis synovial membrane explants : interactions with antiinflammatory cytokines?