Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.
The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.
Katayama
K
K
Department of Internal Medicine, Osaka Kouseinenkin Hospital, 2-2, Yamadaoka, Suita-city, Osaka, Japan.
Kasahara
A
A
Sasaki
Y
Y
Kashiwagi
T
T
Naito
M
M
Masuzawa
M
M
Katoh
M
M
Yoshihara
H
H
Kamada
T
T
Mukuda
T
T
Hijioka
T
T
Hori
M
M
Hayashi
N
N
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D016207:Cytokines / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D012367:RNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D001613:beta 2-Microglobulin / Q000097:blood
D000998:Antiviral Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D016898:Interferon-alpha; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D019798:Neopterin; D007371:Interferon-gamma