J Kountouras1, P Boura, G Tsapas. 1. Department of Medicine, Aristotelian University of Thessaloniki, Greece.
Abstract
BACKGROUND/AIMS: Both rhGM-CSF and IFN-gamma have antiviral and immunoregulatory effects. Furthermore, GM-CSF has the advantage of increasing WBC in leukocytopenic patients. METHODOLOGY: We investigated a) the antiviral effects of rhGM-CSF and INF-alpha combination treatment in 12 chronic hepatitis B patients with leukocytopenia as a result or not of previous interferon therapy, b) the in vivo effects of these agents on monocyte-macrophage and T-lymphocyte functions and, c) their correlation to HBV infection outcome. RESULTS: Combination therapy caused a significant fall in HBV-DNA levels (p<0.0002), accompanied by significant reductions in transaminase levels and in histological activity index (p<0.0001, in each case). In parallel, rhGM-CSF induced a 2.7- to 5-fold weekly increment in WBC. Moreover, treatment caused a significant increase in all monocyte-macrophage parameters (p<0.0001 for random, directed migration and phagocytosis index) and in peripheral blood lymphocyte parameters (p<0.0001 for IL-2r and HLA-DR expression) studied. A similar picture was also obtained from cytokine levels (IL-2 and GM-CSF) in the supernatants from PHA-cultured T-lymphocytes (p<0.0003, <0.001, respectively). CONCLUSIONS: The combined therapy achieves the initial treatment aim of increasing WBC and exerting an antiviral effect. In addition, the observed changes in immunological parameters probably reflect a Th1 pattern of immune response that could be responsible for the fate of HBV infection. Finally, cytokine levels (IL-2 and GM-CSF) in the supernatants might serve to monitor viral activity and outcome of the HBV infection.
BACKGROUND/AIMS: Both rhGM-CSF and IFN-gamma have antiviral and immunoregulatory effects. Furthermore, GM-CSF has the advantage of increasing WBC in leukocytopenic patients. METHODOLOGY: We investigated a) the antiviral effects of rhGM-CSF and INF-alpha combination treatment in 12 chronic hepatitis Bpatients with leukocytopenia as a result or not of previous interferon therapy, b) the in vivo effects of these agents on monocyte-macrophage and T-lymphocyte functions and, c) their correlation to HBV infection outcome. RESULTS: Combination therapy caused a significant fall in HBV-DNA levels (p<0.0002), accompanied by significant reductions in transaminase levels and in histological activity index (p<0.0001, in each case). In parallel, rhGM-CSF induced a 2.7- to 5-fold weekly increment in WBC. Moreover, treatment caused a significant increase in all monocyte-macrophage parameters (p<0.0001 for random, directed migration and phagocytosis index) and in peripheral blood lymphocyte parameters (p<0.0001 for IL-2r and HLA-DR expression) studied. A similar picture was also obtained from cytokine levels (IL-2 and GM-CSF) in the supernatants from PHA-cultured T-lymphocytes (p<0.0003, <0.001, respectively). CONCLUSIONS: The combined therapy achieves the initial treatment aim of increasing WBC and exerting an antiviral effect. In addition, the observed changes in immunological parameters probably reflect a Th1 pattern of immune response that could be responsible for the fate of HBV infection. Finally, cytokine levels (IL-2 and GM-CSF) in the supernatants might serve to monitor viral activity and outcome of the HBV infection.