OBJECTIVESTo explore the roles of CD14 and TLR4 in severe hepatitis B induced by endotoxin.

METHODSThe levels of mCD14 on PBMCs from 30 cases of severe hepatitis B, 20 cases of chronic hepatitis B and 20 cases of healthy controls were detected by flow cytometry. The expressions of CD14 mRNA and TLR4 mRNA in PBMCs from these patients were also detected by RT-PCR. Meanwhile, the concentration of plasma endotoxin was detected by limulus amebocyte lysate test and the levels of TNF alpha, IL-1, IL-6 in serum were detected by ELISA.

RESULTSThe levels of mCD14 on PBMCs in severe hepatitis B, chronic hepatitis B and control were 74.2+/-12.3, 63.6+/-11.8 and 60.3+/-7.2 respectively. There was a significant difference among severe hepatitis B,chronic hepatitis B and healthy controls (both of P less than 0.01). The expressions of CD14 mRNA and TLR4 mRNA (2.92+/-0.67 and 1.86+/-0.45) were also upregulated, compared with that in chronic hepatitis B patients (1.34+/-0.51, 0.93+/-0.18) and healthy group (0.92+/-0.58, 0.73+/-0.16) (P less than 0.01). Similarly, the concentration of plasma endotoxin was much higher in severe hepatitis B (1.87+/-1.61) than that in chronic hepatitis B patients (0.11+/-0.11) and that in healthy group (0.03+/-0.03) (P less than 0.01). As a result, the inflammation cytokines, such as TNF alpha, IL-1 and IL-6 (19.78+/-9.21, 0.96+/-0.16, 68.34+/-48.30) also increased significantly in severe hepatitis B, which were remarkably higher than those in chronic hepatitis B patients (7.26+/-6.52, 0.19+/-0.02 and 19.28+/-4.65) and healthy group (4.15+/-4.06, 0.15+/-0.01 and 12.01+/-3.88) (P less than 0.01). Furthermore, correlation analysis showed there was positive correlation among the level of mCD14, the expression of CD14 mRNA/TLR4 mRNA, the concentration of endotoxin and the levels of inflammation cytokines in severe hepatitis B (r1 = 0.865, r2 = 0.415, r3 = 0.524, all of P less than 0.05).

CONCLUSIONEndotoxin is an important factor in the aggravation of hepatitis B. Meanwhile, mCD14, CD14 mRNA and TLR4 mRNA are remarkably upregulated during the endotoxin stimulation. The inflammation cytokines (TNF alpha, IL-1 and IL-6) are also elevated, which may finally result in the aggravation of the hepatitis B. Therefore, CD14, TLR4 and inflammation cytokines play important roles in pathogenesis of severe hepatitis B induced by endotoxin.