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Enhancement of cutaneous immunity during ageing.

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Dr Anil Ganjoo    04 December 2017

A new study published in The Journal of Allergy and Clinical Immunology investigated changes in tissue specific mechanisms involved in the decreased response to varicella zoster virus (VZV) during ageing.

Here, a VZV antigen challenge system was used to assess cutaneous immunity by the extent of erythema and induration after intradermal VZV antigen injection. Further, immune histology and transcriptomic analyses were performed on skin biopsies from the site of challenge in young subjects below 40 years of age and older subjects above the age of 65 years.

The findings revealed that older individuals exhibited decreased erythema and induration, CD4+ (cluster of differentiation-4) and CD8+ T cell infiltration and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared to young subjects. This was found to be associated with elevated sterile inflammation in the skin in the same subjects, related to p38 mitogen-activated protein kinase (MAPK)-related pro-inflammatory cytokine production. Subsequently, systemic inflammation was inhibited in old subjects by pre-treatment with an oral small molecule p38 MAP kinase inhibitor, which reduced both serum C reactive protein (CRP) and peripheral blood monocyte secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This led to a significant increase in cutaneous responses to VZV antigen challenge in the same individuals.

Hence, it was inferred that excessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. It was stated that this can be reversed by inhibition of inflammatory cytokine production that may be utilized to promote vaccine efficacy and the treatment of infections and malignancy during ageing.

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