title: Efficacy of azithromycin in preventing lethal graft-versus-host disease.
abstract: Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) is initiated by donor T lymphocytes that recognize histocompatibility antigens presented by recipient dendritic cells (DCs). Current approaches to reduce GVHD are focused on suppressing donor T lymphocyte responses to alloantigens. However, these strategies may be inadequate in the setting of allogeneic transplants (particularly histoincompatible transplants), may increase the risk of tumour relapse and are associated with high rates of opportunistic infections. We hypothesized that inhibition of recipient DCs might suppress GVHD. We recently demonstrated in vitro that azithromycin, a macrolide antibiotic, also acts as a nuclear factor (NF)-κB inhibitor of murine DCs and inhibits their maturation and functions, including allogeneic responses. We investigated whether azithromycin could prevent alloreactions in a murine histoincompatibility model. Oral administration of azithromycin to recipient mice for 5 days during major-histoincompatible BMT suppressed lethal GVHD significantly, whereas ex-vivo lymphocyte function was not affected by the drug. These data suggest that azithromycin has potential as a novel prophylactic drug for lethal GVHD.
authors: Department of Pediatrics and Cell Transplantation, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors: S
authors: S
authors: Iwamoto
authors: E
authors: E
authors: Azuma
authors: T
authors: T
authors: Kumamoto
authors: M
authors: M
authors: Hirayama
authors: T
authors: T
authors: Yoshida
authors: M
authors: M
authors: Ito
authors: K
authors: K
authors: Amano
authors: M
authors: M
authors: Ido
authors: Y
authors: Y
authors: Komada
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D016753:Interleukin-10; D017963:Azithromycin
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