Pa. Clavien et al., ACUTE REACTANT CYTOKINES AND NEUTROPHIL ADHESION AFTER WARM ISCHEMIA IN CIRRHOTIC AND NONCIRRHOTIC HUMAN LIVERS, Hepatology, 23(6), 1996, pp. 1456-1463
Animal studies suggest that acute phase reactant cytokines and polymor
phonuclear leukocytes (PR;IN) may play a critical role in ischemia-rep
erfusion injury, To evaluate whether similar mechanisms are operative
in human liver, six cirrhotic and nine noncirrhotic patients undergoin
g right hepatectomy were randomized for utilization of hepatic vascula
r exclusion (HVE) as a model of ischemia-reperfusion injury, Port-al a
nd systemic levels of acute reactant cytokines (interleukin 6 [IL-6],
interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha]) and neu
trophil adhesion in serial liver biopsy specimens were studied, Correl
ations among mediators, leukocyte adhesion, and markers of liver injur
y were also evaluated. Hepatic vascular exclusion resulted in substant
ial and reproducible changes in portal and arterial IL-6 levels in bot
h cirrhotic and noncirrhotic patients, Portal and systemic cytokine le
vels were comparable in most instances, whereas levels were usually hi
gher in cirrhotic patients than in noncirrhotic patients, Negative cor
relations were found between IL-6 levels at the time of reperfusion an
d later TNF-alpha levels, IL-6 levels correlated negatively with numer
ous markers of hepatocellular injury and the number of postoperative c
omplications, Hepatic vascular exclusion increased neutrophils adhesio
n after reperfusion in cirrhotic patients but not in noncirrhotic pati
ents, In cirrhotic patients, the degree of leukocyte adhesion after re
perfusion correlated with several postoperative markers of liver injur
y, This study in humans shows that acute reactant cytokines are releas
ed during liver ischemia and, interestingly, that IL-6 levels strongly
correlate with clinical and laboratory measures of injury. Further st
udies to evaluate possible causal relationship with hepatic injury are
warranted, with emphasis on the role of IL-6 and PMN adhesion.