Impaired hepatic removal of interleukin-6 in patients with liver cirrhosis.
Systemic concentrations of interleukin-6 (IL-6) are elevated in patients with liver cirrhosis, and impaired hepatic uptake of IL-6 was suggested to contribute to higher levels in these patients. To test this hypothesis IL-6 was measured in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 41 patients with liver cirrhosis and four patients with normal liver function. IL-6 was higher in PVS than HVS of all blood donors and about 43% of portal vein derived IL-6 was extracted by the healthy liver, and 6.3% by the cirrhotic liver demonstrating markedly impaired removal of IL-6 by the latter. Whereas in patients with CHILD-PUGH stage A IL-6 in HVS was almost 25% lower than in PVS, in patients with CHILD-PUGH stage C IL-6 was similarly abundant in the two blood compartments. Ascites is a common complication in cirrhotic patients and was associated with higher IL-6 levels in all blood compartments without significant differences in hepatic excretion. Hepatic venous pressure gradient did not correlate with the degree of hepatic IL-6 removal excluding hepatic shunting as the principal cause of impaired IL-6 uptake. Furthermore, patients with alcoholic liver cirrhosis had higher IL-6 in all blood compartments than patients with cryptogenic liver cirrhosis. Aetiology of liver cirrhosis did not affect hepatic removal rate indicating higher IL-6 synthesis in patients with alcoholic liver cirrhosis. In summary, the current data provide evidence that impaired hepatic removal of IL-6 is explained by hepatic shunting and liver dysfunction in patients with liver cirrhosis partly explaining higher systemic levels.
Wiest
Reiner
R
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Weigert
Johanna
J
Wanninger
Josef
J
Neumeier
Markus
M
Bauer
Sabrina
S
Schmidhofer
Sandra
S
Farkas
Stefan
S
Scherer
Marcus N
MN
Schäffler
Andreas
A
Schölmerich
Jürgen
J
Buechler
Christa
C
D000328:Adult; D000368:Aged; D000886:Anthropometry; D001201:Ascites / Q000097:blood / Q000150:complications / Q000503:physiopathology; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000098:blood supply* / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000503:physiopathology
C508600:IL6 protein, human; D015850:Interleukin-6