ObjectiveTo determine the effect of the nitric oxide synthase inhibitor, L-NG-monomethylarginine, on interleukin-6 and interleukin-8 accumulation, and nuclear factor-kappa B expression in an endothelial cell model of sepsis.DesignControlled cell culture experiments examining the immunomodulatory effects of nitric oxide synthase inhibition.SubjectsA human endothelial cell line (EA.hy926).Measurements and ResultsCells were incubated with tumor necrosis factor-alpha and interleukin (IL)-1 beta in the presence of L-NG-monomethylarginine(L-NMMA). IL-6 and IL-8 were measured in culture supernatants using enzyme immunoassay. Nuclear factor-kappa B was measured using electrophoretic mobility shift assay and was quantified using phosphorimaging. IL-6 accumulation was decreased (p < .05) and IL-8 accumulation increased (p < .01) with L-NMMA. Increased nuclear factor-kappa B expression in stimulated cells was unaltered on exposure to L-NMMA. Cell viability was unaffected.ConclusionsExcessive production of nitric oxide has been implicated in septic shock, and the use of nitric oxide synthase inhibitors has been suggested. The immunoregulatory actions of nitric oxide synthase inhibitors affects the profile of cytokine release. This effect is not mediated through modulation of nuclear factor-kappa B. These findings have implications for the use of nitric oxide synthase inhibiting agents in septic shock. (Crit Care Med 1999; 27:908-912)