title: Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.
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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Subhasis
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Samit R
authors.initials: SR
authors.lastname: Joshi
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ueda
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Jean
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Department of Center for Vaccine Development, Saint Louis University, Missouri.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Blevins
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Barbara
authors.initials: B
authors.lastname: Siconolfi
authors.affiliation: Department of Pathology.
authors.forename: Hailong
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Lesley
authors.initials: L
authors.lastname: Devine
authors.affiliation: Department of Neurology.
authors.forename: Khadir
authors.initials: K
authors.lastname: Raddassi
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Sui
authors.initials: S
authors.lastname: Tsang
authors.affiliation: Department of Center for Vaccine Development, Saint Louis University, Missouri.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
authors.affiliation: Department of Neurology Department of Immunobiology.
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.affiliation: Department of Immunobiology.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.affiliation: Department of Pathology Department of Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.affiliation: Department of Internal Medicine, Yale School of Medicine.
authors.forename: Mark
authors.initials: M
authors.lastname: Trentalange
authors.affiliation: Department of Internal Medicine, Yale School of Medicine.
authors.forename: Heather G
authors.initials: HG
authors.lastname: Allore
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000276:immunology / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D055815:Young Adult
chemical_list: D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007252:Influenza Vaccines; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: aging; cytokine; influenza vaccine; innate immunity; monocyte