Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C.
To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).
Fukuda
R
R
Second Department of Internal Medicine, Shimane Medical University, Japan.
Ishimura
N
N
Ishihara
S
S
Chowdhury
A
A
Morlyama
N
N
Nogami
C
C
Miyake
T
T
Niigaki
M
M
Tokuda
A
A
Satoh
S
S
Sakai
S
S
Akagi
S
S
Watanabe
M
M
Fukumoto
S
S
D000328:Adult; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D011994:Recombinant Proteins
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma