Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults

J Infect Dis. 2015 Apr 1;211(7):1174-84. doi: 10.1093/infdis/jiu573. Epub 2014 Nov 2.

Abstract

We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged ≥65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor α and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults.

Keywords: aging; cytokine; influenza vaccine; innate immunity; monocyte.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Dual Specificity Phosphatase 1 / immunology
  • Dual Specificity Phosphatase 1 / metabolism
  • Female
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Innate
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Phosphorylation
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination
  • Young Adult

Substances

  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Influenza Vaccines
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1