PLASMA INTERLEUKIN-6 LEVELS IN PATIENTS WITH CIRRHOSIS - RELATIONSHIPTO ENDOTOXEMIA, TUMOR-NECROSIS-FACTOR-ALPHA, AND HYPERDYNAMIC CIRCULATION

Liver cirrhosis with portal hypertension is associated with hyperdynam ic circulation characterized by generalized vasodilatation and increas ed cardiac output and regional blood flows. Patients with liver cirrho sis present with increased levels of interleukin-6 (IL-6), which may i nhibit vascular smooth-muscle contraction. We investigated whether inc reased plasma IL-6 levels contribute to the pathogenesis of hyperdynam ic circulation observed in cirrhotic patients and whether they are cor related with plasma tumor necrosis factor-alpha (TNF-alpha) and endoto xin concentrations. Methods: In 58 consecutive cirrhotic patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6 we re measured with enzyme-linked immunosorbent assay, and endotoxin dete rminations with a limulus assay. In addition, 52 cirrhotic patients un derwent a hemodynamic study using Swan-Ganz catheterization. Results: Plasma TNF-alpha, IL-6, and endotoxin levels were significantly higher in cirrhotic patients than in healthy subjects (7.3 +/- 0.2 versus 5. 8 +/- 0.1 pg/ml, 6.4 +/- 0.8 versus 2.0 +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01). In cirrhotic patie nts the plasma levels of TNF-alpha, IL-6, and endotoxin progressively increased in relation to the severity of liver dysfunction (graded by Pugh's classification). A significant correlation was observed between plasma TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no co rrelation was observed between plasma endotoxin levels and plasma TNF- alpha and IL-6 levels. Plasma IL-6 levels correlated negatively with s ystemic vascular resistance in patients with cirrhosis (r = 0.5, p < 0 .01). Conclusions: Plasma IL-6 levels are increased in patients with c irrhosis. The severity of liver cirrhosis is an important factor for t he occurrence of increased IL-6 levels. IL-6 may play a role in the hy perdynamic circulation observed in patients with cirrhosis.