Progression of autoimmune-mediated hepatic lesions in a murine graft-versus-host reaction by neutralizing IL-10.
C57BL/6 (B6) spleen T cells which were injected into major histocompatibility complex (MHC) class II-disparate (B6.C-H-2(bm/2)xB6) F1 hybrid mice induced autoimmune graft-versus-host reaction (GVHR). Early production of interferon (IFN)-gamma and delayed production of interleukin (IL)-10 might play an important role in the formation of GVHR hepatic lesions. To clarify whether blocking of IL-10 deteriorate autoimmune-mediated hepatic lesions induced by GVHR, and to elucidate the change of the T helper (Th)1/Th2 cytokines in the liver, anti-IL-10 monoclonal antibodies (mAbs, 500 μg) were given 4 h before the induction of GVHR. We evaluated the change of splenomegaly and GVHR-induced hepatic lesions. The changes of the expressions of IFN-gamma and IL-4 mRNA isolated from liver-infiltrating lymphocytes were measured by real-time polymerase chain reaction (PCR). In GVHR with anti-IL-10 mAbs mice splenomegaly and periportal cellular infiltration was significantly increased compared with those of GVHR mice. In these mice, both IFN-gamma and IL-4 mRNA expression levels were significantly elevated by the neutralization of IL-10. These findings suggest an important role of IL-10 in murine GVHR due to MHC class II disparity. IL-10 may play a crucial role in down-regulating autoimmune-related hepatic lesions.
Unno
Rie
R
Division of Gastroenterology and Hepatology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Ibaraki 305-8575, Tsukuba, Japan
Matsuzaki
Yasushi
Y
Itoh
Shinichi
S
Doy
Mikio
M
Shoda
Junichi
J
Tanaka
Naomi
N