The role of lipoxygenases in endotoxin-induced cytokine production.

The LPS induced synthesis of tumor necrosis factor in macrophage cultures, as determined in a fibroblast cytolysis assay was found to be effectively blocked by inhibitors of lipoxygenases. Likewise, the presence of tumor necrosis factor in serum of D-galactosamine sensitized mice after challenge with endotoxin was suppressed by the lipoxygenase inhibitors. From LPS-treated macrophages 13-hydroxylinoleic acid, a lipoxygenase product was isolated, which is significantly increased after LPS treatment of the cells, covalently bound to cellular constituents and was found to counterbalance the suppression of TNF-synthesis by a lipoxygenase inhibitor when added to macrophages exogenously.