Spontaneous production of tumour necrosis factor alpha and interleukin-1 beta during interferon-alpha treatment of chronic HBV infection.
Seven chronic carriers of hepatitis B virus (HBV) were studied during treatment with interferon-alpha to determine whether tumour necrosis factor alpha (TNF alpha) or interleukin-1 beta (IL-1 beta) contributed to the elimination of HBV. Four patients responded to interferon-alpha with clearance of HBeAg and permanent inhibition of HBV replication within 3-12 weeks; in each of these patients, the changes were accompanied by substantial rises in spontaneous in-vitro production of TNF alpha and IL-1 beta by peripheral blood mononuclear cells from previously undetectable levels. There was little or no change in spontaneous TNF alpha and IL-1 beta production in the three patients who did not lose HBeAg in response to interferon-alpha. These findings suggest that TNF alpha and IL-1 beta may contribute to the permanent elimination during interferon-alpha treatment of hepatocytes supporting viral infection and that the therapeutic potential of these cytokines is worthy of investigation.
Daniels
H M
HM
Liver Unit, King's College Hospital, London, UK.
Meager
A
A
Eddleston
A L
AL
Alexander
G J
GJ
Williams
R
R
D000328:Adult; D002353:Carrier State / Q000097:blood / Q000382:microbiology / Q000628:therapy*; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis; D004341:Drug Evaluation; D005500:Follow-Up Studies; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000096:biosynthesis*; D053583:Interleukin-1beta; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D007370:Interferon Type I; D007375:Interleukin-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171)