title: Dietary fish oil supplementation alters LTB4:LTB5 ratios but does not affect the expression of acute graft versus host disease in mice.
abstract: One of the mechanisms by which corticosteroids may modify acute graft vs host disease (GvHD) is via inhibition of arachidonic acid (AA) metabolism. Leukotriene B4 (LTB4) is a product of that pathway which may take part in the pathogenesis of GvHD through the stimulation of T-lymphopoiesis and T-lymphocyte activation. LTB4 is a metabolite of AA (20:4n-6). Alternate dietary sources of polyunsaturated fatty acids (PUFA), specifically eicosapenteinoic acid (20:5n-3) (EPA) and docosahexaenoic acid (22:6n-3) (DHA), shift the LTs formed with a decrease in LTB4 an increase in LTB5. LTB5 is a less potent agonist than LTB4 and this results in a theoretical decrease of LTB4 mediated events. Supplementation of in vitro bone marrow cultures with EPA or DHA had no detrimental effect on myeloid colony formation. Dietary EPA/DHA supplementation in mice with induced GvHD appeared to be safe and well tolerated. The LTB4:LTB5 ratio shifted from 7.65 +/- 1.75 in control-fed animals to 1.03 +/- 0.18. Fish-oil-supplementation did not compromise engraftment or stem cell content. Alone, this therapy was unable to modify GvHD.
authors.affiliation: Division of Medical Oncology, College of Medicine, University of Florida, Gainesville 32610-0277.
authors.forename: A M
authors.initials: AM
authors.lastname: Miller
authors.forename: D W
authors.initials: DW
authors.lastname: van Bekkum
authors.forename: S M
authors.initials: SM
authors.lastname: Kobb
authors.forename: M B
authors.initials: MB
authors.lastname: McCrohan
authors.forename: S
authors.initials: S
authors.lastname: Knaan-Shanzer
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000178:diet therapy* / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D005395:Fish Oils; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015118:Eicosapentaenoic Acid; D008084:Lipoxygenase