Omega-3 from fish oil augments GVHD through the enhancement of chemotherapy conditioning regimen and selective FoxP3 depletion

Abstract

Omega-3 is known to enhance the effects of several chemotherapeutic agents and to exert several immunoregulatory actions In the present study, we evaluated the effects of a 21-day feeding regimen with omega-3-rich fish oil (FO) and its corresponding control, omega-6 rich corn oil (CO), on the BU-CY conditioning and the development of GVHD after BMT in mice. Before conditioning, FO, but not CO, feeding caused a significant attenuation in the number and functionality of splenic FoxP3 þ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b þ myeloid cells in both the BM and spleen. Consequently, FO-fed animals conditioned with BU-CY showed exacerbated GVHD following transplantation with allogeneic BM and splenic cells. In contrast, identical transplantation in CO-fed mice resulted in poor engraftment and body weight loss. Moreover, in standard-fed recipients, BMT with cells from FO-fed donors resulted in moderate GVHD and improved the survival time, whereas BMT with cells from CO-fed donors shortened the survival time and caused anemia. We conclude that food supplements should be considered in patients undergoing BMT and/or chemotherapy treatment.

From support to therapy: rethinking the role of nutrition in acute graft-versus-host disease

“…The potential effects of EFAs on GVHD have been explored in a B6→Balb/c mouse model of allogeneic HSCT with a chemotherapy-based conditioning regimen. Interestingly, omega-3-rich fish oil supplementation worsens GVHD by reducing the reconstitution of regulatory T cells ( 57 ). The precise role of dietary fatty acids in GVHD warrants further investigation.…”

Personalized Treatment: The Future of Medicine. A Perspective on the Preconditioning for Stem Cell Transplantation

“…11 The bioavailability of these drugs is correlated with several factors including age of the patient, genetic make-up, gut function, gut flora, and types of ingested food, in addition to the chemical and physical properties of the drug. 17,18 In a multicentric phase III clinical trial, low doses of cytostatics were compared to higher doses with regard to the outcome of SCT and survival. The study was permanently halted as higher doses were clearly associated with a better prognosis.…”