Basic and clinical immunology
Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-γ

https://doi.org/10.1016/j.jaci.2005.12.1322Get rights and content

Background

N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development.

Objective

We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed.

Methods

We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-γ; n = 167) secretion in a US birth cohort.

Results

Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-γ levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-γ levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-γ levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-γ level.

Conclusion

Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-γ secretion.

Clinical implications

The implications of these findings for allergy or asthma development are not yet known.

Section snippets

Subjects

Subjects for this study were a subgroup of participants from Project Viva, a pregnancy and birth cohort study underway in eastern Massachusetts. Enrollment for this study occurred from April 1999 through July 2002. Expectant mothers were approached at their initial prenatal visit for consent. Participants were interviewed and completed questionnaires in the first and second trimesters of pregnancy, as well as at the time of delivery. Umbilical venous cord blood was obtained at the time of

Results

In this population the gestational age ranged from 30.9 to 42.1 weeks (Table I). Maternal smoking was rare. Of the mothers, 11% were obese, with a BMI of greater than 30 kg/m2. Maternal obesity was associated with lower n-3 EPA levels in cord plasma. The median cord EPA level was 0.86 percentage points for children of mothers with a BMI of greater than 30 kg/m2 compared with a median level of 0.97 percentage points for children of mothers with a BMI of 30 kg/m2 or less. Only 6 of 192 children

Discussion

In this US birth cohort study, we found that both higher levels of cord blood n-3 EPA and n-6 AA were associated with attenuation of cord blood lymphocyte proliferation and decreased IFN-γ secretion in response to allergen stimulation. The evidence for independent effects of both EPA and AA on attenuated immune responses was stronger for IFN-γ than for SI (lymphoproliferative response). Although n-3 EPA and n-6 AA had similar inverse associations with SI and IFN-γ, the ratio of AA/EPA also

Cited by (0)

Supported by National Institutes of Health grants R01 HL61907, HD34568, HL64925, HL68041, and AI/EHS35786.

Disclosure of potential conflict of interest: M. Gillman has received grant support from Mead Johnson Nutritionals. No Conflict of Interest disclosure statement was received from C. Schroeter. The rest of the authors have declared they have no conflict of interest.

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