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Antimicrobial Agents and Chemotherapy, February 2005, p. 590-599, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.590-599.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

Patrizia Carotenuto,¹ Debby van Riel,^1,2 André Artsen,¹ Sven Bruijns,¹ Fons G. Uytdehaag,^1, Jon D. Laman,² Andeltje B. van Nunen,³ Pieter E. Zondervan,⁴ Robert A. De Man,³ Albert D. Osterhaus,¹ and Oscar Pontesilli^1*

Institute of Virology,¹ Department of Immunology,² Department of Gastroenterology,³ Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands⁴

Received 16 June 2004/ Returned for modification 10 September 2004/ Accepted 6 October 2004

To investigate whether therapy with alpha interferon (IFN-) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN- 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- treatment. In contrast, CD14 was weakly expressed in the absence of IFN- 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- differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-, 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- 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.

Present address: Crucell, Leiden, The Netherlands.