Reduced interleukin-12, interleukin-18, and interferon-gamma production with prolonged rat hepatic allograft survival after donor-specific blood transfusion.
Interferon-gamma is a key immunoregulatory cytokine involved in acute graft rejection. Immunologic unresponsiveness to organ allografts has been induced by pretransplantation donor-specific blood transfusion, both experimentally and clinically. We investigated interferon-gamma production and intragraft gene expression of type-1 T-helper cytokines such as interleukin-12 and -18 and type-2 T-helper cytokines such as interleukin-10 and transforming growth factor-beta in rats receiving hepatic allografts after such transfusions. The animals were divided into four groups: group I received isografts; group II received allografts; group III received allografts after donor-specific transfusion; and group IV received allografts and was treated with FK 506. Donor blood given seven days prior to transplantation significantly prolonged allograft survival. The serum interferon-gamma concentrations in group II increased, peaking on day 5 and then decreasing. Serum interferon-gamma concentrations in groups I, III, and IV were significantly lower than those observed in group II, as were levels of interleukin-12 and interleukin-18 mRNA in the graft. Transforming growth factor-beta and interleukin-10 mRNA levels in grafts in transfused animals were significantly greater than those in the untreated allograft group. Interleukin-12 and -18 mRNA transcripts in an allogeneic mixed lymphocyte reaction were inhibited by interleukin-10 and transforming growth factor-beta. These results suggest that interleukin-12 and -18 expression in hepatic allografts is inhibited in the immunologically unresponsive state induced by donor-specific transfusion.
Department of Surgery II, Kumamoto University Medical School, Japan.
Y
Y
Yamaguchi
F
F
Matsumura
J
J
Liang
E
E
Akizuki
T
T
Matsuda
K
K
Okabe
H
H
Ohshiro
K
K
Ishihara
S
S
Yamada
K
K
Mori
M
M
Ogawa
D000818:Animals; D001803:Blood Transfusion / Q000379:methods*; D006085:Graft Survival; D007165:Immunosuppression Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma