Expression of IFN-inducible protein-10 in chronic hepatitis.
Chemokines such as IFN-inducible protein-10 (IP-10) and JE/monocyte chemotactic protein-1 (MCP-1) are induced in the murine liver in a tissue-specific manner. We examined whether IP-10 and MCP-1 are pathologically involved in chronic hepatitis. Whereas the serum levels of IP-10 and MCP-1 in patients with chronic persistent hepatitis C were elevated compared with those in normal volunteers, both chemokine levels were further significantly higher in patients with the active form (chronic active hepatitis (CAH)). The elevated IP-10 level was not a general phenomenon of inflammation, because it was not seen in patients with rheumatoid arthritis, whereas MCP-1 levels were elevated to the same extent in both patient groups. Better responsiveness to IFN therapy in CAH was related to lesser grades of necroinflammatory activity and was predicted by the lower IP-10 and higher MCP-1 levels. IP-10 levels in patients cured by IFN therapy decreased to the levels in normal volunteers, while the MCP-1 levels only slightly decreased. Serum levels of both chemokines in patients who were not cured remained unchanged after IFN therapy. In situ hybridization analysis of CAH revealed that IP-10 mRNA was expressed mainly in hepatocytes around intralobular focal and periportal piecemeal necrosis, while some MCP-1 mRNA was expressed in some sinusoidal cells. These results suggested that IP-10 plays a specific role in the intralobular accumulation of mononuclear cells and/or the death of hepatocytes in chronic hepatitis.
Narumi
S
S
Pharmaceutical Basic Research Laboratories, Japan Tobacco, Inc. Central Pharmaceutical Research Institute, Yokohama, Kanagawa, Japan.
Tominaga
Y
Y
Tamaru
M
M
Shimai
S
S
Okumura
H
H
Nishioji
K
K
Itoh
Y
Y
Okanoue
T
T
D018932:Chemokine CCL2 / Q000097:blood*; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D017403:In Situ Hybridization; D020382:Interleukin-18; D008099:Liver / Q000276:immunology* / Q000473:pathology
D018932:Chemokine CCL2; D016207:Cytokines; D020382:Interleukin-18