Effect of L-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNFα 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 levels of interleukin (IL) IL-6, IL-8, tumor necrosis factor-alpha (TNFα) and nitrite/nitrate (NO₂^-/ NO₃^-) in patients with severe septic shock. Design: Prospective clinical study. Setting: Surgical intensive care unit at a university hospital. Patients: 11 consecutive patients with severe septic shock. Interventions: Standard hemodynamic measurements were made and blood samples taken at intervals before, during, and after a 12-h infusion of L-NAME 1 mg·kg^-1 h^-1 for determination of plasma IL-6, IL-8, TNFα and NO₂^-/NO₃^- concentration. Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα and NO₂^-/NO₃^- (p < 0.05). Plasma levels of IL-6, IL-8, and NO₂^-/NO₃^- were negatively correlated with systemic vascular resistance (r = -0.62, r = -0.65, and r = -0.78, respectively, all p < 0.05). Continuous infusion of L-NAME increased mean arterial pressure and systemic vascular resistance, with a concomitant reduction in cardiac output (all p < 0.01). No significant changes were seen in levels of plasma IL-6, IL-8, and NO₂^-/NO₃^- during the 24-h observation period. Plasma levels of TNFα were significantly reduced during the L-NAME infusion compared to baseline (p < 0.05). Conclusions: NO plays a role in the cardiovascular derangements of human septic shock. Inhibition of NO synthesis with L-NAME does not promote excessive cytokine release in patients with severe sepsis.