Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis

Objective: Nitric oxide has been proposed as a mediator of hyperdynamic cir culation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitr ic oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and t o correlate these findings with clinical, biochemical, and hemodynamic para meters. Methods: Clinical, biochemical, and hemodynamic parameters were ass essed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin -l, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nit rites were determined. Results: Mean arterial pressure was lower and interl eukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotox in positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with w orsening of Child score (p < 0.005). Patients with ascites had higher level s of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients with out (p, < 0.001); this association was independent of the severity of liver disease. II patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor a and nitrates-nitrites levels were not diff erent. By multivariate analysis, high interleukin-6 levels showed independe nt associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations w ith Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r greater than or equal to 0.4, p < 0.005). Conclusions: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other f actors are involved. Interleukin-6, possibly through nitric oxide-independe nt mechanisms, also might play a role in the vasodilatation of cirrhosis an d the pathogenesis of hepatic encephalopathy. (C) 1999 by Am. Cell. of Gast roenterology.