Evidence for a deficiency of interferon response in mononuclear cells from hepatitis C viremic patients.
OBJECTIVE
The pathophysiology of chronic hepatitis C and the mechanisms of resistance to interferon alpha are poorly understood. The aim of this work was to assess the influence of HCV infection and the viral genotype on lymphocyte production of 2',5' oligo-adenylate synthetase activity and monocyte production of TNF alpha and IL1 beta.


METHODS
Mononuclear cells from 50 consecutive patients were studied after 6 months of interferon treatment. Patients with persistent viremia (PCR-positive, elevated ALT, n = 39) were compared with the PCR-negative patients with normal ALT activity (n = 11) of similar age and sex ratio.


RESULTS
Cells from the viremic patients showed lower basal and stimulated 2',5' oligo-adenylate synthetase activity, and a lower in vitro response capacity to human recombinant interferon. In contrast, no difference was observed in basal and stimulated TNF alpha or IL1 beta production between the two groups. In the PCR-positive patients the viral genotype had no significant influence on the response of mononuclear cells to interferon or endotoxin.


CONCLUSIONS
These results show that the presence of HCV in blood is associated with an elective defect in interferon system activation, independently of the viral genotype.
Podevin
P
P
INSERM U402, Laboratoire de biochimie A, Hôpital Saint-Antoine, Paris, France.
Guechot
J
J
Serfaty
L
L
Monrand-Joubert
L
L
Veyrunes
C
C
Bonnefis
M T
MT
Poupon
R
R
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D012016:Reference Values; D014766:Viremia / Q000378:metabolism* / Q000473:pathology*
D000998:Antiviral Agents; D016207:Cytokines; D011994:Recombinant Proteins; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase