title: The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response.
abstract: BACKGROUND
  Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy.
  
  
  METHODS
  110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR.
  
  
  RESULTS
  The median age of the patients was 16 years (range 3-60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05).
  
  
  CONCLUSIONS
  Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects.
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Varpu
authors.initials: V
authors.lastname: Elenius
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid (UCM), Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Palomares
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Turunen
authors.affiliation: Department of Otorhinolaryngology, Turku University Hospital, Turku, Finland.|Department of Otorhinolaryngology, Satakunta Central Hospital, Pori, Finland.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Puhakka
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: Beate
authors.initials: B
authors.lastname: Rückert
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Tytti
authors.initials: T
authors.lastname: Vuorinen
authors.affiliation: Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Allander
authors.affiliation: Department of Biostatistics, University of Turku, Turku, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Vahlberg
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.affiliation: Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States of America.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Jartti
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000097:blood / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000821:virology; D007113:Immunity, Innate / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008297:Male; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000097:blood; D014066:Palatine Tonsil / Q000276:immunology / Q000601:surgery / Q000821:virology; D012141:Respiratory Tract Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D014068:Tonsillectomy; D014801:Vitamin A / Q000097:blood*; D014807:Vitamin D / Q000097:blood*; D014810:Vitamin E / Q000097:blood*; D055815:Young Adult; D054804:Cathelicidins
chemical_list: D000485:Allergens; D023181:Antimicrobial Cationic Peptides; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508587:IL37 protein, human; D007375:Interleukin-1; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D014801:Vitamin A; D014807:Vitamin D; D014810:Vitamin E; D007073:Immunoglobulin E; D007371:Interferon-gamma; D054804:Cathelicidins