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- Title
Disulfiram, an Anti-alcoholic Drug, Targets Macrophages and Attenuates Acute Rejection in Rat Lung Allografts.
- Authors
Nobuyuki Yoshiyasu; Rei Matsuki; Masaaki Sato; Hirokazu Urushiyama; Etsuko Toda; Yasuhiro Terasaki; Masaki Suzuki; Aya Shinozaki-Ushiku; Yuya Terashima; Jun Nakajima
- Abstract
Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an antialcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280-300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-β-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No posttransplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression.
- Subjects
DISULFIRAM; MONOCYTE chemotactic factor; LABORATORY rats; HOMOGRAFTS; LUNGS
- Publication
Transplant International, 2024, p1
- ISSN
0934-0874
- Publication type
Article
- DOI
10.3389/ti.2024.12556