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Reduced Interleukin-12, Interleukin-18, and Interferon-γ Production with Prolonged Rat Hepatic Allograft Survival After Donor-Specific Blood Transfusion

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Abstract

Interferon-γ 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-γ 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-β 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-γ concentrations in group II increased, peaking on day 5 and then decreasing. Serum interferon-γ 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-β 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-β. These results suggest that interleukin-12 and -18 expression in hepatic allografts is inhibited in the immunologically unresponsive state induced by donor-specific transfusion.

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Authors and Affiliations

  1. Department of Surgery II, Kumamoto University Medical School, Kumamoto

    Yasuo Yamaguchi, Fujio Matsumura, Jian Liang, Eiji Akizuki, Teishi Matsuda, Kazutoshi Okabe, Hajime Ohshiro, Kohjiro Ishihara, Shinwa Yamada, Katsutaka Mori & Michio Ogawa

  2. The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Yasuo Yamaguchi, Fujio Matsumura, Jian Liang, Eiji Akizuki, Teishi Matsuda, Kazutoshi Okabe, Hajime Ohshiro, Kohjiro Ishihara, Shinwa Yamada, Katsutaka Mori & Michio Ogawa

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  1. Yasuo Yamaguchi
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Yamaguchi, Y., Matsumura, F., Liang, J. et al. Reduced Interleukin-12, Interleukin-18, and Interferon-γ Production with Prolonged Rat Hepatic Allograft Survival After Donor-Specific Blood Transfusion. Dig Dis Sci 45, 2429–2435 (2000). https://doi.org/10.1023/A:1005659529472

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