In vivo effect of granulocyte-macrophage colony-stimulating factor and interferon combination on monocyte-macrophage and T-lymphocyte functions in chronic hepatitis B leukocytopenic patients

BACKGROUND/AIMS: Both rhGM-CSF and IFN-gamma have antiviral and immunoregul atory effects. Furthermore, GM-CSF has the advantage of increasing WBC in l eukocytopenic patients. METHODOLOGY: We investigated a) the antiviral effects of rhGM-CSF and INF-a lpha combination treatment in 12 chronic hepatitis B patients with leukocyt openia as a result or not of previous interferon therapy, b) the in, vivo e ffects of these agents on monocyte-macrophage and T-lymphocyte functions an d, 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 c aused a significant increase in all monocyte-macrophage parameters (p<0.000 1 for random, directed migration and phagocytosis index) and in peripheral blood lymphocyte parameters (p<0.0001 for IL-2r and HLA-DR expression) stud ied. 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 inc reasing WBC and exerting an antiviral effect. In addition, the observed cha nges in immunological parameters probably reflect a Th1 pattern of immune r esponse that could be responsible for the fate of HBV infection. Finally, c ytokine levels (IL-2 and GM-CSF) in the supernatants might serve to monitor viral activity and outcome of the HBV infection.