EFFECT OF L-NAME, AN INHIBITOR OF NITRIC-OXIDE SYNTHESIS, ON PLASMA-LEVELS OF IL-6, IL-8, TNF-ALPHA AND NITRITE NITRATE IN HUMAN SEPTIC SHOCK/

Objectives: We tested the effects of N-G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on plasma leve ls of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNF al pha) and nitrite/nitrate (NO2-/ NO3-) in patients with severe septic s hock. Design: Prospective clinical study. Setting: Surgical intensive care unit at a university hospital. Patients: 11 consecutive patients with severe septic shock. Interventions: Standard hemodynamic measurem ents were made and blood samples taken at intervals before, during, an d after a 12-h infusion of L-NAME 1 mg.kg(-1).h(-1) for determination of plasma IL-6, IL-8, TNF alpha and NO2-/NO3- concentration. Measureme nts and results: Patients with sepsis had increased plasma levels of I L-6, IL-8, TNF alpha and NO2-/NO3- (p<0.05), Plasma levels of IL-6. IL -8: and NO2-/NO3- were negatively correlated with systemic vascular re sistance (r = -0.62, r = -0.65, and r = -0.78, respectively, all p < 0 .05). Continuous infusion of L-NAME increased mean arterial pressure a nd systemic vascular resistance, with a concomitant reduction in cardi ac output (all p < 0.01). No significant changes were seen in levels o f plasma IL-6, IL-8, and NO2-/NO3- during the 24-h observation period. Plasma levels of TNF alpha were significantly reduced during L-NAME i nfusion compared to baseline (p < 0.05), Conclusions: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition o f NO synthesis with L-NAME does not promote excessive cytokine release in patients with severe sepsis.