An analysis of acute changes in interleukin-6 levels after treatment of hepatitis C with consensus interferon.
Cytokine production has been implicated in the antiviral response to interferon-alpha (IFN-alpha) in hepatitis C and in the development of IFN-alpha-related side effects. We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN (IFN-con1) and during continuous treatment of chronic hepatitis C patients. Serum samples were collected at baseline, at multiple times early after IFN administration, and weekly thereafter. Viral RNA titers were assessed by RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, and IL-16. Serum cytokine levels were low at baseline. IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR, indicating that low levels of circulating IL-6 were associated with hepatitis C infection. None of the cytokines measured increased significantly after IFN administration except for IL-6. IL-6 levels rose rapidly, peaked at 6-15 h in a dose-dependent manner, and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment. This was confirmed by RT-PCR. Pretreatment IL-6 levels were directly correlated with area under the curve (AUC) for IL-6 during the 24 h after IFN dosing (r = 0.611, p = 0.007). Viral titers decreased within 24-48 h after a single dose of IFN-con1. Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels. In conclusion, (1) baseline serum cytokine levels, except for IL-6, were low or within the normal range in patients with hepatitis C, (2) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls, (3) IL-6 levels increased acutely after a single dose of IFN-alpha, and IL-6 induction was related to baseline IL-6 level, and (4) changes in IL-6 levels did not correlate with the early virologic response to IFN.
Cotler
S J
SJ
Section of Hepatology and Department of Preventive Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Reddy
K R
KR
McCone
J
J
Wolfe
D L
DL
Liu
A
A
Craft
T R
TR
Ferris
M W
MW
Conrad
A J
AJ
Albrecht
J
J
Morrissey
M
M
Ganger
D R
DR
Rosenblate
H
H
Blatt
L M
LM
Jensen
D M
DM
Taylor
M W
MW
D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D007700:Kinetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins
D000998:Antiviral Agents; D016207:Cytokines; D007370:Interferon Type I; D016898:Interferon-alpha; D015850:Interleukin-6; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; C050739:interferon alfacon-1