Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603
2001; Elsevier BV; Volume: 97; Issue: 4 Linguagem: Inglês
10.1182/blood.v97.4.1123
ISSN1528-0020
AutoresYue Lü, Sumio Sakamaki, Hiroyuki Kuroda, Toshiro Kusakabe, Yuichi Konuma, Takehide Akiyama, Akihito Fujimi, Naofumi Takemoto, Kyokusen Nishiie, Takuya Matsunaga, Yasuo Hirayama, Junji Kato, Shinichiro Kon, Katsuhisa Kogawa, Yoshiro Niitsu,
Tópico(s)Immune Cell Function and Interaction
ResumoAbstract Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-γ or tumor necrosis factor-α have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4+ helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.
Referência(s)