Favorable effect of adefovir on the number and functionality of myeloid dendritic cells of patients with chronic HBV.
In patients with chronic hepatitis B virus (HBV), 2 predominant precursor dendritic cell (DC) subtypes, the myeloid dendritic cell (mDC) and the plasmacytoid dendritic cell (pDC), were recently found to be functionally impaired. HBV DNA was found to be present in the DC subtypes, but no viral replication could be detected. The question remains whether simply the presence of the virus and viral proteins causes this dysfunction of DCs. To address this issue, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the number and functionality of circulating DCs was studied during 6 months of treatment. Treatment resulted in a mean 5 log(10) decrease in the viral load and normalization of alanine aminotransferase within 3 months. The number of mDCs, but not of pDCs, increased significantly over 6 months of treatment to a level comparable to that of uninfected healthy controls. The allostimulatory capacity of isolated and in vitro matured mDCs increased significantly after 3 months of treatment. Accordingly, mDCs exhibited an increased capacity to produce tumor necrosis factor alpha and interleukin-12 after 3-6 months of treatment. There was no change in interferon alpha production by pDCs during treatment. In conclusion, adefovir treatment results in an improvement in the number and functionality of mDCs, but not of pDCs. Our findings provide clues for the reasons why current antiviral therapy does not lead to consistently sustained viral eradication.
van der Molen
Renate G
RG
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. R.vandermolen@erasmusmc.nl
Sprengers
Dave
D
Biesta
Paula J
PJ
Kusters
Johannes G
JG
Janssen
Harry L A
HL
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load
D015703:Antigens, CD; D000998:Antiviral Agents; D016207:Cytokines; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D063065:Organophosphonates; C053001:adefovir; D000410:Alanine Transaminase; D000225:Adenine