Cytokine production in patients with cirrhosis and TLR4 polymorphisms

AIM:To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.METHODS:The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms,and 10 wild-type patients matched for age,sex and degree of liver failure.TLR4 polymorphisms were determined by sequence-based genotyping.Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide(LPS)and lipoteichoic acid(LTA)stimulation.RESULTS:Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients(78%vs 20%,P=0.02).Spontaneous production of interleukin(IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients[IL-6:888.7(172.0-2119.3)pg/m L vs 5540.4(1159.2-26053.9)pg/m L,P<0.001;IL-10:28.7(6.5-177.1)pg/m L vs 117.8(6.5-318.1)pg/m L,P=0.02].However,the production of tumor necrosis factor-α,IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups.CONCLUSION:TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients,suggesting that they play a role in the development of cirrhosis complications.