Induction of IL-1Ra in resistant and responsive hepatitis C patients following treatment with IFN-con1.
Hepatitis C virus (HCV) infection is resistant to interferon-alpha (IFN-alpha) in some patients. The mechanism of this resistance is unknown. Interleukin-1 receptor antagonist (IL-1Ra) is induced by IFN-alpha and is a good indicator of IFN activity. In the current study, we compared IL-1Ra levels in rapid virologic responders and flat responders who showed resistance to IFN. Three groups of patients were examined, including those who received a single dose of consensus IFN (IFN-con1), patients who received daily IFN-con1 for 1 week, and patients who received IFN-con1 daily for 24 weeks. Serum IL-1Ra, IL-6, and HCV RNA were measured serially in all groups. Serum IL-1Ra levels increased rapidly in all patients with hepatitis C after IFN-alpha administration, irrespective of their virologic response. IL-1Ra levels remained elevated at 1 week but were similar to baseline by week 2 of treatment in patients receiving continuous therapy. IL-6 levels also increased acutely but rose more slowly than IL-1Ra levels. The increase in IL-1Ra and IL-6 observed in both flat and rapid virologic responders indicates that IFN receptors are functioning in patients with IFN-resistant hepatitis C and that the lack of response is related to other virologic or immunologic factors.
Cotler
Scott J
SJ
Section of Hepatology and Department of Preventive Medicine, RUSH-Presybterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Craft
Teresa
T
Ferris
Mary
M
Morrisey
Mary
M
McCone
Jonathan
J
Reddy
K Raj
KR
Conrad
Andrew
A
Jensen
Donald M
DM
Albrecht
Jeff
J
Taylor
Milton W
MW
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000097:blood; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology
D000998:Antiviral Agents; C507763:IL1RN protein, human; D007370:Interferon Type I; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D012367:RNA, Viral; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C050739:interferon alfacon-1