The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

PLoS One. 2017 Feb 24;12(2):e0172350. doi: 10.1371/journal.pone.0172350. eCollection 2017.


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.

MeSH terms

  • Adolescent
  • Adult
  • Allergens / blood
  • Allergens / immunology
  • Antimicrobial Cationic Peptides / blood*
  • Cathelicidins
  • Child
  • Female
  • Forkhead Transcription Factors / blood
  • Humans
  • Hypersensitivity / blood*
  • Hypersensitivity / virology
  • Immunity, Innate / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interferon-gamma / blood
  • Interleukin-1 / blood
  • Interleukin-17 / blood
  • Male
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / blood
  • Palatine Tonsil / immunology
  • Palatine Tonsil / surgery
  • Palatine Tonsil / virology
  • Respiratory Tract Infections / blood
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / virology
  • Tonsillectomy
  • Vitamin A / blood*
  • Vitamin D / blood*
  • Vitamin E / blood*
  • Young Adult


  • Allergens
  • Antimicrobial Cationic Peptides
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL37 protein, human
  • Interleukin-1
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Vitamin A
  • Vitamin D
  • Vitamin E
  • Immunoglobulin E
  • Interferon-gamma
  • Cathelicidins

Grant support

This work was supported by Terveyden Tutkimuksen Toimikunta 114034 and 132595 (to Tuomas Jartti), Tampereen Tuberkuloosisäätiö (to Varpu Elenius), Suomen Lääketieteen Säätiö (to Varpu Elenius), Sigrid Juséliuksen Säätiö (to Tuomas Jartti), European Social Fund (to Oscar Palomares), EU Framework Program Predicta (to Mübeccel Akdis), Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 260895 (to Cezmi A Akdis), and Christine Kuhne-Center for Allergy Research and Education (to Cezmi A Akdis).