Immunolocalisation of interferon-alpha in hepatitis C patients and its correlation with response to interferon-alpha therapy.
Localised interferon-alpha production was investigated in hepatitis C patients entered into a trial of interferon-alpha-2a therapy. Antibodies capable of reacting specifically with interferon-alpha-2, interferon-alpha-4 or with all interferon-alpha subtypes were used as immunohistochemical and immunofluorescence probes to study interferon-alpha production in liver biopsy tissue, and peripheral blood mononuclear cells prior to and after stimulation with Sendai virus. Measurement of cytoplasmic interferon-alpha, specifically interferon-alpha-2 and interferon-alpha-4, in peripheral blood mononuclear cells isolated from the hepatitis C patients and of total interferon-alpha secreted into culture supernatants by these cells showed interferon-alpha production similar to that of peripheral blood mononuclear cells isolated from normal individuals. Interferon-alpha-positive cells were observed in the infiltrating mononuclear cells of the liver biopsy tissue obtained from 8 of the 14 patients. Lymphocytes, fibroblasts, Kupffer cells, polymorphonuclear cells and monocytes stained positive for interferon-alpha, and specifically interferon-alpha-4, in all of the eight patients. The cytoplasm of hepatocytes also stained weakly positive in three of these patients. Interferon-alpha positive cells showed a good correlation with the degree of histological damage observed in the liver biopsies but not with presence of antibodies towards hepatitis C virus or levels of serum alanine aminotransferase measured prior to interferon-alpha-2a therapy. Interestingly, response to therapy seemed linked to local interferon-alpha production status. Those patients who responded best to therapy displayed no or only low levels of interferon-alpha positive cells in liver biopsy tissue. Thus patients with a lower activation of their endogenous interferon-alpha system may benefit from administration of exogenous interferon-alpha.
Greenway
A L
AL
Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
Hertzog
P J
PJ
Devenish
R J
RJ
Dudley
F J
FJ
McMullen
G L
GL
Linnane
A W
AW
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006526:Hepatitis C / Q000097:blood / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D014018:Tissue Distribution; D016896:Treatment Outcome
D015415:Biomarkers; D016898:Interferon-alpha