Vitamin D3 replacement enhances antigen-specific immunity in older adults.

Emma S Chambers,Gabriele Pollara,Malcolm Rustin,Adrian R Martineau,Milica Vukmanovic-Stejic,Tom C Freeman,Hugh Trahair,Arne N Akbar,Evdokia Tsaliki,Mahdad Noursadeghi,Neil A Mabbott,Carolin T Turner,Barbara B Shih

doi:10.1093/immadv/ltaa008

Abstract

SummaryIntroductionAgeing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing.ObjectivesWe investigated the use of vitamin D3 replacement to enhance cutaneous antigen-specific immunity in older adults (≥65 years).MethodsVitamin D insufficient older adults (n = 18) were administered 6400IU of vitamin D3/day orally for 14 weeks. Antigen-specific immunity to VZV was assessed by clinical score assessment of the injection site and transcriptional analysis of skin biopsies collected from challenged injection sites pre- and post-vitamin D3 replacement.ResultsWe showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D3 supplementation significantly increased the response to cutaneous VZV antigen challenge in older adults. This enhancement was associated with a reduction in inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site of antigen challenge in the skin.ConclusionVitamin D3 replacement can boost antigen-specific immunity in older adults with sub-optimal vitamin D status.

Highlights

Immunity decreases during ageing as demonstrated by the increased susceptibility to bacterial and viral infections, re-activation of latent infections such as varicella zoster virus (VZV), decreased vaccine efficacy, and increased incidence of cancer [1,2,3]
Vitamin D3 replacement can boost antigen-specific immunity in older adults with suboptimal vitamin D status
We have shown that intradermal injections of air, saline, or antigen into the skin of older adults are associated with induction of an early non-specific inflammation which directly contributes to reduced cutaneous immunity [12]

Summary

Introduction

Immunity decreases during ageing as demonstrated by the increased susceptibility to bacterial and viral infections, re-activation of latent infections such as varicella zoster virus (VZV), decreased vaccine efficacy, and increased incidence of cancer [1,2,3]. There is an increase in low-grade systemic inflammation in older humans termed inflammageing. We have shown that intradermal injections of air, saline, or antigen into the skin of older adults are associated with induction of an early non-specific inflammation which directly contributes to reduced cutaneous immunity [12]. We proposed that this non-specific inflammation is driven by senescent fibroblasts recruiting inflammatory monocytes that secrete PGE2 and directly inhibit antigenspecific immunity [12]. Blockade of inflammation using the anti-inflammatory drug Losmapimod (a specific p38 MAP kinase inhibitor) can restore antigen-specific immunity in older adults via inhibition of the non-specific inflammation in the skin [8, 12]

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Conclusion