title: Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection.
abstract: Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)₂D₃, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)₂D₃ significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold,p= 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold,p= 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p= 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)₂D₃ may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. edwin.hoe@mcri.edu.au.
authors.forename: Edwin
authors.initials: E
authors.lastname: Hoe
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. jordan.nathanielsz@mcri.edu.au.
authors.forename: Jordan
authors.initials: J
authors.lastname: Nathanielsz
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. zheng.quantoh@mcri.edu.au.
authors.forename: Zheng Quan
authors.initials: ZQ
authors.lastname: Toh
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. leena.spry@mcri.edu.au.
authors.forename: Leena
authors.initials: L
authors.lastname: Spry
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. rachel.marimla@mcri.edu.au.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marimla
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. anne.balloch@mcri.edu.au.
authors.forename: Anne
authors.initials: A
authors.lastname: Balloch
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. kim.mulholland@lshtm.ac.uk.|London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK. kim.mulholland@lshtm.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Mulholland
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia. paul.licciardi@mcri.edu.au.|Department of Paediatrics, The University of Melbourne, Parkville VIC 3010, Australia. paul.licciardi@mcri.edu.au.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Licciardi
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000276:immunology*; D002117:Calcitriol / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D013296:Streptococcus pneumoniae; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000097:blood / Q000276:immunology*; D014815:Vitamins / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D008024:Ligands; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D016753:Interleukin-10; D007371:Interferon-gamma; D002117:Calcitriol
keywords: bacterial infection; inflammation; pneumococcal; vitamin D