Backgrounds/aims: Serum concentrations of macrophage-colony stimulating factor (M-CSF) are increased in parallel with hepatic inflammation. The aim of this study was to assess the immunologic significance of elevated M-CSF in patients with chronic hepatitis B virus infection.
Methods: The subjects included 20 asymptomatic HBV carriers and 45 patients with chronic hepatitis B, including 8 undergoing prednisolone treatment, 10 experiencing an acute exacerbation, and 12 undergoing daily administration of interferons.
Results: Serum concentrations of M-CSF significantly decreased during prednisolone administration, but significantly increased following prednisolone withdrawal, similar to the increase during acute exacerbation. Changes in the lipopolysaccharide-stimulated production of interleukin-1-beta and tumor necrosis factor-alpha by peripheral whole blood, or of interferon-gamma by peripheral blood mononuclear cells showed a similar pattern. Serum concentrations of M-CSF did not correlate with the titers of HBV-DNA or HBV-DNA polymerase activity. However, serum M-CSF peaked preceding seroconversion to HBe antibody in three HBe antigen positive patients. Exogenous interferon-alpha, -beta, or -gamma induced significant elevation in serum M-CSF concentrations, irrespective of changes in the serum alanine aminotransferase levels.
Conclusions: Increased serum M-CSF is closely associated with increased serum interferons and/ or proinflammatory cytokines produced by peripheral blood cells during hepatic inflammation in chronic hepatitis B. This may be a consequence of the altered cytokine cascade resulting from the host immune response against hepatitis B virus.