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 (NO 2 − /NO 3 − ) 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 NO 2 − /NO 3 − concentration. Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα, and NO 2 − /NO 3 − (p<0.05). Plasma levels of IL-6, IL-8, and NO 2 − /NO 3 − 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 NO 2 − /NO 3 − during the 24-h observation period. Plasma levels of TNFα were significantly reduced during 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.