Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women.
BACKGROUND
Altered intakes of n-3 and n-6 polyunsaturated fatty acids were suggested to modulate allergic disease, but intervention trials yielded inconclusive results. Because allergies are primed in early infancy and in utero, the fetus might be more accessible to nutritional intervention strategies.


OBJECTIVE
We sought to investigate how supplementation of pregnant women with a fish oil (FO) preparation modulates allergy-related immune parameters in mothers and offspring.


METHODS
We performed a multicenter, randomized, double-blind, placebo-controlled trial. Three hundred eleven pregnant women received daily either FO with 0.5 g of docosahexaenoic acid and 0.15 g of eicosapentaenoic acid, 400 mug of methyl-tetra-hydrofolic acid, both, or placebo from the 22nd gestational week. T(H)1/T(H)2-related molecules were quantified in 197 maternal and 195 cord blood samples by using real-time RT-PCR. Data are given as geometric means [95% CIs].


RESULTS
FO supplementation was associated with increased TGF-beta mRNA in maternal (0.85 [0.8-0.89]; placebo: 0.68 [0.64-0.72]) and cord blood (0.85 [0.81-0.9]; placebo: 0.75 [0.71-0.79]). IL-1 (0.69 [0.66-0.73]; placebo: 0.83 [0.79-0.88]) and IFN-gamma (0.54 [0.51-0.57]; placebo: 0.65 [0.61-0.69]) were decreased in mothers only (P < .001). Cord blood mRNA levels of IL-4 (0.54 [0.52-0.57]; placebo: 0.64 [0.61-0.68]), IL-13 (0.61 [0.58-0.65]; placebo: 0.85 [0.80-0.89]), CCR4 (0.70 [0.67-0.73]; placebo: 0.88 [0.84-0.92]; all P < .001), and natural killer (P < .001) and CCR3+CD8+ T cells (P < .04) were decreased in the FO group.


CONCLUSIONS
Supplementation with FO during pregnancy is associated with decreased mRNA levels of T(H)2-related molecules in the fetus and decreased maternal inflammatory cytokines. We speculate that both effects are mediated by TGF-beta.
Krauss-Etschmann
Susanne
S
Clinical Cooperation Group "Pediatric Immune Regulation," Children's Hospital of Ludwig-Maximilians-University and GSF-National Research Center for Environment and Health, Neuherberg, Germany. susanne.krauss-etschmann@med.uni-muenchen.de
Hartl
Dominik
D
Rzehak
Peter
P
Heinrich
Joachim
J
Shadid
Rania
R
Del Carmen Ramírez-Tortosa
María
M
Campoy
Cristina
C
Pardillo
Susana
S
Schendel
Dolores J
DJ
Decsi
Tamás
T
Demmelmair
Hans
H
Koletzko
Berthold V
BV
D000328:Adult; D016207:Cytokines / Q000097:blood; D036861:Delivery, Obstetric; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood; D005395:Fish Oils / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood; D018793:Interleukin-13 / Q000097:blood* / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood* / Q000235:genetics; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D011247:Pregnancy / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D054398:Receptors, CCR4 / Q000097:blood* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics
C515354:CCR4 protein, human; D016207:Cytokines; D005395:Fish Oils; D018836:Inflammation Mediators; D018793:Interleukin-13; D012333:RNA, Messenger; D054398:Receptors, CCR4; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D004281:Docosahexaenoic Acids