RT Journal Article
SR Electronic
T1 Mechanisms of endotoxin tolerance in patients with alcoholic liver cirrhosis: role of interleukin 10, interleukin 1 receptor antagonist, and soluble tumour necrosis factor receptors as well as effector cell desensitisation
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 281
OP 287
DO 10.1136/gut.47.2.281
VO 47
IS 2
A1 V von Baehr
A1 W-D Döcke
A1 M Plauth
A1 C Liebenthal
A1 S Küpferling
A1 H Lochs
A1 R Baumgarten
A1 H-D Volk
YR 2000
UL http://gut.bmj.com/content/47/2/281.abstract
AB BACKGROUND In patients with alcoholic liver cirrhosis, endotoxaemia is a frequent finding. Unknown mechanisms, however, prevent typical clinical symptoms of endotoxaemia in many patients.METHODS We determined plasma levels of pro- and anti-inflammatory mediators, ex vivo cytokine secretion capacity, and expression of tumour necrosis factor (TNF) receptors on phagocytic blood cells in 49 patients with alcoholic cirrhosis and 41 age matched healthy controls.RESULTS In addition to increased levels of proinflammatory cytokines in cirrhotic patients, we observed consistent upregulation of the anti-inflammatory mediators interleukin 10 (IL-10) (plasma 15.75 (1.6) v6.6 (1.3) pg/ml (p<0.001); ex-vivo 108.4 (22.0)v 40.1 (7.4) pg/ml (p<0.05)), interleukin 1 receptor antagonist (plasma 527.1 (83) v331.4 (56) pg/ml (p<0.05); ex vivo 19.9 (3.4)v 10.2 (2.7) ng/ml (p<0.01)), and soluble TNF receptors (sTNF-R) in plasma (sTNF-RI 3157.2 (506.2)v 607.9 (300.3) pg/ml; sTNF-RII 3331.0 (506.2) v 1066.4 (225.1) pg/ml (p<0.001 for both)). Desensitisation at the target cell level was indicated by reduced expression of TNF receptor I on granulocytes (64.8 (6.5)v 40.1 (7.3)% positive cells; p<0.05) and unaltered plasma levels of soluble E-selectin.CONCLUSION In patients with alcoholic liver cirrhosis, upregulation of the pro- and anti-inflammatory cytokine system and simultaneous desensitisation of effector cells could explain the restricted systemic inflammatory response to chronic endotoxaemia. This alteration in immune status may lead to impairment of host defences against infections which are frequent complications of alcoholic cirrhosis.ILinterleukinIL-1raIL-1 receptor antagonistLPSlipopolysaccharideTNFtumour necrosis factorsTNF-Rsoluble TNF receptorsE-selectinsoluble E-selectinSIRSsystemic inflammatory response syndromeASTaspartate aminotransferaseALTalanine aminotransferaseGGTgamma glutamyltransferasePBSphosphate buffered salineIFN-γinterferon γ