Dietary fish oil supplementation alters LTB4:LTB5 ratios but does not affect the expression of acute graft versus host disease in mice.
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.
Miller
A M
AM
Division of Medical Oncology, College of Medicine, University of Florida, Gainesville 32610-0277.
van Bekkum
D W
DW
Kobb
S M
SM
McCrohan
M B
MB
Knaan-Shanzer
S
S
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
D005395:Fish Oils; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015118:Eicosapentaenoic Acid; D008084:Lipoxygenase