title: 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+ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b+ 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.
authors.affiliation: Experimental Cancer Medicine (ECM), Department for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Al Hashmi
authors.forename: B
authors.initials: B
authors.lastname: Sadeghi
authors.forename: Z
authors.initials: Z
authors.lastname: Hassan
authors.forename: M
authors.initials: M
authors.lastname: Abedi-Valugerdi
authors.forename: M
authors.initials: M
authors.lastname: Lindskog
authors.forename: M
authors.initials: M
authors.lastname: Hassan
mesh_terms: D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000382:microbiology*; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse