SUPPRESSIVE EFFECT OF HEPATITIS-B VIRUS ON THE INDUCTION OF INTERLEUKIN-1-BETA AND INTERLEUKIN-6 GENE-EXPRESSION IN THE THP-1 HUMAN MONOCYTIC CELL-LINE

The major target organ for Hepatitis B Virus (HBV) is the liver, but e xtrahepatic sites including monocytes express receptors for HBV and ma y become infected, Therefore, we investigated the effect of HBV on the in vitro expression of interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) by the monocytoid cell line THP-1, exposed to various stimuli (LPS, PMA or both), Nonstimulated THP-1 cells did not synthesize IL-1 beta and IL-6, even after in vitro exposure to HBV, LPS stimulation al one induced moderate secretion of both IL-1 beta and IL-6 (300 pg/ml), After induction of macrophage differentiation by PMA, THP-1 cells acq uired adherence and expressed a higher level of IL-1 beta (up to 2 ng/ ml) but did not synthesize IL-6. Treatment of THP-1 cells with PMA and LPS caused the highest production of both IL-1 beta and IL-6 (> 5ng/m l), In vitro exposure of PMA+LPS-stimulated THP-1 cells to HBV resulte d in secretion of both HBsAg and preS2Ag which was maintained over 10 days of culture, Southern blot technique was used to study the state o f HBV DNA in the cells, Hybridization of non-digested cellular DNA sho wed only high molecular weight HBV DNA forms, The HindIII restriction pattern revealed bands corresponding to large DNA fragments and the pr esence of bands at the 3.2 kb position, Under these conditions (PMA+LP S), HBV inhibited the production of IL-1 beta and IL-6 proteins and co mpletely suppressed the IL-1 beta and IL-6 mRNA, Thus, our findings (i ) strongly support a relationship between the state of cell differenti ation and susceptibility of cells to HBV infection, and (ii) demonstra te that HBV exerts an inhibitory effect on the induction of IL-1 beta and IL-6 genes expression in monocytic THP-1 cells, These results sugg est that HBV leads to a fall of pro-inflammatory cytokine production b y monocytes/macrophages, which may contribute to impaired host immune response during infection.