Breast Milk Fatty Acids May Link Innate and Adaptive Immune Regulation: Analysis of Soluble CD14, Prostaglandin E2, and Fatty Acids

Abstract

In addition to its role in sensing intraluminal microbial antigens, soluble (s)CD14 may regulate immune responses by its lesser known function as a lipid carrier with possible influences in the production of fatty acid-derived eicosanoids. We investigated the interrelations of fatty acids, prostaglandin E 2 (PGE 2 ), and sCD14 and their role in infant atopic eczema during the first year of life. Serum and breast milk samples from mothers and serum samples from their infants were collected at infant's age 3 mo and analyzed for sCD14 and PGE 2 concentrations and for fatty acid compositions. The main correlation of sCD14 was with arachidonic acid (20:4n-6) (AA). Dihomo-␥-linolenic acid (20:3n-6) (DHGLA) and the ratio of n-6 to n-3 fatty acids correlated positively and docosahexaenoic acid (22:6n-3) (DHA) and sum of n-3 fatty acid negatively with PGE 2 in mother's serum and linoleic acid (LA) negatively with PGE 2 in breast milk. Soluble CD14 tended to be higher and LA, total polyunsaturated fatty acid (PUFA), and sum of n-6 fatty acids were lower in breast milk received by infants with atopic eczema compared with those without. These results suggest that fatty acids contribute to the regulation of innate and adaptive immune responses and link intraluminal exposures, mother's diet, and microbes. C haracteristic dietary habits in Western societies have constantly been linked to chronic diseases such as diabetes, cardiovascular diseases, and more recently allergic diseases. The accumulating data point to the early fetal period and infancy as the critical phase (1). Specific dietary compounds, including fatty acids and probiotics, have been exploited in the development of prophylactic and therapeutic interventions, the effects ensuing through their immunomodulatory properties (2). For the infant, the effects are drawn together by outstanding breast milk composition, providing not only nourishment but also signals for the maturation of the adaptive immune responses considered imperative with regard to the risk of diseases (3).Although the major function described for soluble (s)CD14, a pattern recognition receptor, is binding of lipopolysaccharides and thus antimicrobial host defense (4), its binding specificity is not restricted to bacteria. It also binds phospholipids, thus providing a lipid transfer system (5). This innovative function of sCD14 may prove significant, with a potential to modify immune events through phospholipid polyunsaturated fatty acids (PUFAs). Both dietary and cellular fatty acids are evidently important immune regulators via their derivative eicosanoids, particularly PGE 2 and consequent cytokine responses, as suggested in allergic disease (6). The concentration of sCD14 in breast milk has been shown to be up to 20-fold higher than in serum (7), thus providing infants with an external source of sCD14 with potential health benefits as previously observed in allergic disease (8). Experimental studies have linked sCD14 to phospholipid transport in blood (5,9) and a positive correlation be...

A Meta-Analysis of Randomized, Placebo-Controlled Clinical Trials of Efamol® Evening Primrose Oil in Atopic Eczema. Where Do We Go from Here in Light of More Recent Discoveries?

“…In support of this concept, at least one study has linked high omega-3 long chain polyunsaturated fatty acid (LC-PUFA) content of breast milk with increased risk of atopy in breastfed infants [54]. Another, has correlated potential immunomodulators sCD14 and PGE 2 and its fatty acid precursors (GLA, DGLA and AA) in breast milk with manifestation of infant's atopic eczema which suggest their protective role [52]. Contrary to this is an intervention study where fish oil supplementation during pregnancy was positively associated with CD34+ cells and IL-5-responsive Eo/B-CFU in cord blood and improved one year clinical outcome [55].…”

“…AA is a precursor to prostaglandin E2 (PGE 2 ) which is normally considered to be pro-inflammatory, but perhaps surprisingly to some, it also has a beneficial role in allergic response through its effects on T helper 3 or T regulatory cells and subsequently anti-inflammatory transforming growth factor 2 and interleukin-10 production [52]. Evidence does exist to suggest that the primary defect in atopic eczema might concern the maturation and differentiation of T cells which infiltrate the skin and/or control of T cell infiltration of the skin [53].…”

“…The previous two statements, which appear contrary to one another, may not be so if one also considers other variables such as the milk content of total omega-6 metabolites in the later study. Supporting this consideration, is a follow up study by the same research group which measured lower total PUFAs and sum of omega-6 fatty acids in breast milk received by infants with atopic eczema compared to those without the condition [52]. A review of studies pertaining to fatty acid composition of human milk has concluded that it is dependent on the time of lactation not only during a breast meal but also the time of day and the period of lactation, which may also explain discrepancies in conclusions regarding the relationship between milk fatty acids and atopic disease [62].…”

Prenatal Docosahexaenoic Acid Supplementation and Infant Morbidity: Randomized Controlled Trial

“…n-3 PUFA may influence fetal and infant immune function development in utero, via breast milk, or by a combination of both prenatal and postnatal factors. 42 Additional studies that are designed specifically to examine the influence of perinatal n-3 PUFA nutriture on infant immune function and include both biologically and clinically relevant outcomes are necessary to evaluate the potential value of dietary modification or n-3 PUFA supplementation during pregnancy and/or lactation.…”

CD14: A Soluble Pattern Recognition Receptor in Milk

“…Interestingly, human milk sCD14 levels correlate with those of specific fatty acids (Dunstan et al, 2004;Laitinen et al, 2006) and are influenced by fish oil supplementation in the maternal diet (Dunstan et al, 2004). In bovine milk, sCD14 levels are elevated during mastitis or following intramammary challenge with LPs or Escherichia coli (Bannerman et al, 2003;Lee et al, 2003a, b;Vangroenweghe et al, 2004) and may be due to infiltration of neutrophils to the inflamed mammary gland.…”