Relationship between response to interferon-alpha and function of peripheral blood mononuclear cells in chronic hepatitis C patients.
The factors responsible for the low response of chronic hepatitis C patients to interferon-a treatment are not fully understood, although it is known that interferon requires an efficient host immune response to achieve viral clearance. This study was designed to test the hypothesis that hepatitis C virus infection is associated with functional impairment of peripheral blood mononuclear cells, which influence the response to interferon. The proliferative and apoptotic responses of peripheral blood mononuclear cells and purified T cells stimulated with polyclonal mitogenic signals were assessed in 35 chronic hepatitis C patients and 30 healthy controls. Patients were divided into responders and nonresponders according to their sustained response to a course of alpha-interferon-a (3 MU three times weekly for 12 months). The proliferative response to polyclonal mitogens (PHA, TPA) was significantly decreased in nonresponders compared to responders and controls. The defective response was partially normalized by the exogenous addition of interleukin-2 or interleukin-4, and cannot be ascribed to increased apoptosis. Interestingly, the proliferative response of enriched T cells to the same signals was normal. In conclusion, the clinical response to interferon-a defines two different patterns of proliferation by mononuclear cells in chronic hepatitis C patients. This suggests that an alteration of the immune system in these patients may underlie their inadequate response to antiviral therapy.
Esquivel
Fatima
F
Department of Medicine, Hospital Principe de Asturias, University of Alcalá, Madrid, Spain.
Albillos
Agustín
A
Carrión
Flavio
F
Prieto
Alfredo
A
Reyes
Eduardo
E
Martínez-Martin
Belén
B
Calleja
José Luis
JL
Cacho
Guillermo
G
Alvarez-Mon
Melchor
M
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019233:Retreatment; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D003470:Culture Media; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins