Cytokine release of peripheral blood mononuclear cells in children with chronic hepatitis B virus infection

Background: Immune response to hepatitis B virus (HBV) antigens or mitogens in Asian children with chronic HBV infection who are mainly perinatally in fected has not been studied in connection with the production of various cy tokines, although these patients are considered to be less responsive to an tiviral therapy. Methods: The production of the cytokines interferon (IFN)-gamma, lymphotoxi n, interleukin (IL)-4, tumor necrosis factor (TNF)a, and interleukin (IL)-1 beta by peripheral blood mononuclear cells (PBMCs) was studied in 17 hepat itis B surface antigen (HBsAg) carrier children with raised alanine transfe rase levels (group 1), 17 HBsAg carrier children with normal alanine transf erase levels (group 2), and 20 healthy noncarrier control subjects (group 3 ). Results: Hepatitis B core antigen (HBcAg)-stimulated IFN-gamma production w as significantly higher in group 1 than in groups ? and 3, serum HBeAg clea red within 1 year in five of eight children in group 1 with stimulation ind exes higher than 3, and HBcAg-induced IL-4 secretion was minimal in all gro ups. Interferon-gamma produced by PBMCs stimulated by purified HBsAg did no t differ among the three groups. Higher lymphotoxin production by PBMCs sti mulated by HBcAg was also noted in groups 1 and 2 than in group 3. Lipopoly saccharide (LPS)stimulated TNF-alpha production by PBMCs was significantly higher in group 1 than in group 2. There was no association between HBeAg-a nti-HBe status and production of various cytokines. No differences were see n in the profile of cytokines induced by HBV antigens or LPS in children of carrier mothers compared with children of HBsAg-negative mothers. Conclusion: Increased IFN-gamma production resulting from HBcAg-specific T- helper lymphocyte type 1 response, and increased TNF-alpha production may c ontribute to cell-mediated antiviral immune response in children with chron ic hepatitis B. In HBV carrier children, the ability to produce the studied cytokines is related to whether an endogenous immune attempt to eliminate HBV infection emerges in the patients but is not related to the different m odes of acquisition of HBV infection.