Toshihiro Okamoto (1), Yoshihisa Nakano (1), Wataru Asakura (1), Tadashi
Kobayashi (1), Naoki Tsuzuike (2) and Kaoru Hara (1)
(1) Research Laboratories, Nippon Chemiphar Co., Ltd., 1-22 Hikokawato,
Misato, Saitama 341-0005, Japan
(2) Zeria Pharmaceutical Co., Ltd., 2512-1 Konan-Machi, Ohsato-gun, Saitama
360-0111, Japan
Abstract: The liver injury in the concanavalin A (Con A)-induced
mouse hepatitis model has been well studied. However, there has been little
study on the effects of Con A on extrahepatic organs. The aim of the present
work was to determine the effects of Con A on the spleen, kidney and lung.
A histopathological study showed that Con A (15 mg/kg, i.v.) administration
affects not only the liver, but also all these extrahepatic organs. Messenger
RNA expression was studied by the using polymerase chain reaction. Treatment
with Con A induced interleukin-2 mRNA in the spleen, but only slightly induced
it in the kidney. The mRNAs of interferon-gamma (IFN-gamma) and tumor necrosis
factor-alpha (TNF-alpha) were induced in all these organs. At 24 hr after
Con A treatment, the expression of IFN-gamma mRNA, but not that of TNF-alpha
mRNA, was inhibited by cyclosporine A (50 mg/kg, i.p.), suggesting that
Con A induced these cytokine mRNAs through different mechanisms. In the
kidney and lung, CD4+ and CD8+ T-cell infiltration
was suggested by the Con A-induced CD4 and CD8 mRNAs. The present study
showed the histopathological effects of Con A and Con A-induced cytokine
mRNA expression on the spleen, kidney and lung.
Keywords: Concanavalin A, Cytokine mRNA, Extrahepatic organ, Hepatitis,
Polymerase chain reaction