Radhakrishnan, Sabarinath Venniyil and Palaniyandi, Senthilnathan and Mueller, Gunnar and Miklos, Sandra and Hager, Max and Spacenko, Elena and Karlsson, Fridrik J. and Huber, Elisabeth and Kittan, Nicolai A. and Hildebrandt, Gerhard C. (2015) Preventive Azithromycin Treatment Reduces Noninfectious Lung Injury and Acute Graft-versus-Host Disease in a Murine Model of Allogeneic Hematopoietic Cell Transplantation. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 21 (1). pp. 30-38. ISSN 1083-8791, 1523-6536
Full text not available from this repository. (Request a copy)Abstract
Noninfectious lung injury and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant morbidity and mortality. Azithromycin is widely used in allogeneic HCT recipients for pulmonary chronic GVHD, although current data appear controversial. We induced GVHD and noninfectious lung injury in lethally irradiated B6D2F1 mice by transplanting bone marrow and splenic T cells from allogeneic C57BL/6 mice. Experimental groups were treated with oral azithromycin starting on day 14 until the end of week 6 or week 14 after transplantation. Azithromycin treatment resulted in improved survival and decreased lung injury; the latter characterized by improved pulmonary function, reduced peribronchial and perivascular inflammatory cell infiltrates along with diminished collagen deposition, and a decrease in lung cytokine and chemokine expression. Azithromycin also improved intestinal GVHD but did not affect liver GVHD at week 6 early after transplantation. At week 14, azithromycin decreased liver GVHD but had no effect on intestinal GVHD. In vitro, allogeneic antigen-presenting cell (APC)- dependent T cell proliferation and cytokine production were suppressed by azithromycin and inversely correlated with relative regulatory T cell (Treg) expansion, whereas no effect was seen when T cell proliferation occurred APC independently through CD3/CD28-stimulation. Further, azithromycin reduced alloreactive T cell expansion but increased Treg expansion in vivo with corresponding downregulation of MHC II on CD11c(+) dendritic cells. These results demonstrate that preventive administration of azithromycin can reduce the severity of acute GVHD and noninfectious lung injury after allo-HCT, supporting further investigation in clinical trials. (C) 2015 American Society for Blood and Marrow Transplantation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IDIOPATHIC-PNEUMONIA-SYNDROME; BONE-MARROW-TRANSPLANTATION; BRONCHIOLITIS OBLITERANS SYNDROME; DONOR T-CELLS; ALVEOLAR MACROPHAGES; CONTROLLED-TRIAL; EXACERBATIONS; RECRUITMENT; RECIPIENTS; INFECTION; Acute graft-versus-host disease; Azithromycin; Noninfectious lung injury; Regulatory T cell |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 10:52 |
| Last Modified: | 02 Aug 2019 10:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6328 |
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