Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function.
BACKGROUND
The effect of a docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on human leukocyte function was investigated.


METHODS
Ten male volunteers were supplemented with 3g/day FO containing 26% eicosapentaenoic acid (EPA, 20:5, n-3) and 54% DHA (22:6, n-3) for 2 months.


RESULTS
FO supplementation changed the fatty acid (FA) composition of leukocytes resulting in an increase of n-3/n-6 ratio from 0.18 to 0.62 in lymphocytes and from 0.15 to 0.70 in neutrophils. DHA-rich FO stimulated an increase in phagocytic activity by 62% and 145% in neutrophils and monocytes, respectively. Neutrophil chemotactic response was increased by 128%. The rate of production of reactive oxygen species by neutrophils was also increased, as it was with lymphocyte proliferation. These changes were partially reversed after a 2-month wash out period. With respect to cytokine production by lymphocytes, interleukin (IL)-4 release was not altered, whereas secretions of IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were raised. These results are in contrast to those described by others using EPA-rich FO supplementation. Lymphocyte pleiotropic gene expression was analyzed by a macroarray technique. Of the analyzed genes (588 in total), 77 were modified by the supplementation. FO supplementation resulted in up-regulation of 6 genes (GATA binding protein 2, IL-6 signal transducer, transforming growth factor alpha, TNF, heat shock 90kDa protein 1-alpha and heat shock protein 70kDa 1A) and a down regulation of 71 genes (92.2% of total genes changed). The largest functional group of altered genes was that related to signaling pathways (22% of the total modified genes).


CONCLUSIONS
Therefore, although EPA and DHA are members of n-3 FA family, changes in the proportion of DHA and EPA exert different effects on neutrophil, monocyte and lymphocyte function, which may be a result of specific changes in gene expression.
Gorjão
Renata
R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900, Butantã, São Paulo, SP, Brazil. renatag@icb.usp.br
Verlengia
Rozangela
R
Lima
Thais Martins de
TM
Soriano
Francisco Garcia
FG
Boaventura
Maria Fernanda Cury
MF
Kanunfre
Carla Christine
CC
Peres
Carmem Maldonado
CM
Sampaio
Sandra Concuzzo
SC
Otton
Rosemari
R
Folador
Alessandra
A
Martins
Edgair Fernandes
EF
Curi
Tania Cristina Pithon
TC
Portiolli
Erica Paula
EP
Newsholme
Philip
P
Curi
Rui
R
D000328:Adult; D002455:Cell Division; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005395:Fish Oils; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008297:Male; D008563:Membrane Lipids / Q000032:analysis / Q000737:chemistry; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D024502:alpha-Tocopherol / Q000008:administration & dosage
D005395:Fish Oils; D016209:Interleukin-8; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D024502:alpha-Tocopherol