Antiviral treatment with alpha interferon up-regulates CD14 on liver macrophages and its soluble form in patients with chronic hepatitis B.
To investigate whether therapy with alpha interferon (IFN-alpha) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-alpha from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-alpha treatment. In contrast, CD14 was weakly expressed in the absence of IFN-alpha and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-alpha differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-alpha, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8(+) T cells. These findings show that IFN-alpha is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.
Carotenuto
Patrizia
P
Institute of Virology, Erasmus Medical Center, Dr. Molewaterplein 40, Room L363, 3015 GD Rotterdam, The Netherlands.
van Riel
Debby
D
Artsen
André
A
Bruijns
Sven
S
Uytdehaag
Fons G
FG
Laman
Jon D
JD
van Nunen
Andeltje B
AB
Zondervan
Pieter E
PE
De Man
Robert A
RA
Osterhaus
Albert D
AD
Pontesilli
Oscar
O
D000998:Antiviral Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D019259:Lamivudine / Q000627:therapeutic use; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D016753:Interleukin-10; D019259:Lamivudine