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

• Published in: Intensive care medicine Vol. 24; no. 7; p. 673
• Main Authors: Avontuur, J A; M, Stam, T C, Eggermont, A M; M, Braining, H A, Jongen-lavrencic, M, van Amsterdam, J G; C
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.07.1998
• Subjects: Angina pectoris; Blood pressure; Cytokines; Endothelium; Hemodynamics; Hospitals; Hypotension; Intensive care; Nitrates; Nitric oxide; Plasma; Pulmonary arteries; Sepsis; Surgery; Tumor necrosis factor-TNF; Veins & arteries; Ventilators; Netherlands
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s001340050643

Objectives: We tested the effects of N^sup 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^sub 2^^sup -^/NO^sub 3^^sup -^) 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^sup -1^ ·h^sup -1^ for determination of plasma IL-6, IL-8, TNFα and NO^sub 2^^sup -^/NO^sub 3^^sup -^ concentration. Measurements and results: Patients with sepsis had increased plasma levels of IL-6, IL-8, TNFα, and NO^sub 2^^sup -^/NO^sub 3^^sup -^ (p<0.05). Plasma levels of IL-6, IL-8, and NO^sub 2^^sup -^/NO^sub 3^^sup -^ 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^sub 2^^sup -^/NO^sub 3^^sup -^ 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.[PUBLICATION ABSTRACT]