Abstract

Low maternal dietary vitamin E (but not vitamin C) intake during pregnancy has been associated with increased in vitro cord blood mononuclear cell (CBMC) proliferative responses, childhood wheezing and asthma. We investigated whether these associations reflect direct effects of vitamin E by investigating the effects of supplementing CBMC cultures with physiological concentrations of vitamin E. CBMC from seventy neonates were cultured supplemented with either nothing, α-tocopherol or ascorbic acid. Proliferative, IFN-γ, IL-4, IL-10 and TGF-β responses were measured. In general, vitamin E supplementation was associated with a trend for reduced proliferative responses after stimulation with antigens and house dust mite, and with increased proliferation after stimulation with timothy grass allergen. There was a trend for CBMC cultures to exhibit decreased secretion of IFN-γ, IL-10 and IL-4. Supplementation with vitamin C had no effect on CBMC proliferation, but increased IFN-γ and IL-4 production, and decreased IL-10 production. In conclusion, in vitro vitamin E and C supplementation of CBMC modifies neonatal immune function, but not in a manner predicted by observational epidemiological studies. The observed associations between vitamin E and childhood respiratory disease are complex, and the nature and form of nutritional intervention need to be carefully considered before inclusion in trials.

Highlights

  • The prevalence of asthma and atopic disease has risen dramatically in recent decades and it has been hypothesised that declining dietary antioxidant intake has contributed to the increase [1,2].In vitro data support this notion by demonstrating that antioxidant deficiency can promote T-helper (Th) cell differentiation towards the Th2 phenotype [3,4,5]

  • Direct supplementation of cord blood mononuclear cell (CBMC) with vitamin E was associated with decreased proliferative responses to purified protein derivative μg/mL (PPD), keyhole limpet haemocyanin (KLH) and HDM, there was an opposite effect on proliferation to the allergen Timothy grass pollen extract (TG)

  • TG responses excludes the possibility that any suppressive effects of vitamin E supplementation represent toxicity, which was avoided by adding physiological concentrations representative of those measured in cord blood at birth in the epidemiological study demonstrating an association between vitamin E and CBMC responses [18]

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Summary

Introduction

The prevalence of asthma and atopic disease has risen dramatically in recent decades and it has been hypothesised that declining dietary antioxidant intake has contributed to the increase [1,2].In vitro data support this notion by demonstrating that antioxidant deficiency can promote T-helper (Th) cell differentiation towards the Th2 phenotype [3,4,5]. The prevalence of asthma and atopic disease has risen dramatically in recent decades and it has been hypothesised that declining dietary antioxidant intake has contributed to the increase [1,2]. Trials of antioxidant supplementation of adults with atopic disease suggest minimal clinical benefit [6]. This is not unexpected in the light of recognition that early life factors are important in the immunopathogenesis of atopic disease, with compartmentalisation of allergen specific Th cell immunity into adult equivalent Th1 and Th2 patterns occurring in most children before the age of 5 years [7]. Three birth cohort studies have reported reduced maternal dietary vitamin E intake during pregnancy to be associated with an increased likelihood of childhood wheezing [9,10] and asthma [11]

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