Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals

Clin Exp Immunol. 2011 Apr;164(1):72-9. doi: 10.1111/j.1365-2249.2010.04315.x. Epub 2011 Feb 16.


The immune modulating capacity of vitamin D(3) is well-recognized. Ultra-violet (UV) exposure determines production of vitamin D(3) in vivo and varies through the course of the year, especially in temperate regions. However, it is not known whether the human innate immune response differs due to seasonality. To validate the seasonal effects of vitamin D(3) , the effect of 1,25(OH)(2) D(3) on peripheral blood mononuclear cells (PBMC) cytokine response was first determined in vitro. 1,25(OH)(2) D(3) decreased interleukin (IL)-6 and tumour necrosis factor (TNF)-α release by PBMC stimulated with tripalmitoyl-S-glycerylcysteine (Pam3Cys) or lipopolysaccharide (LPS). Subsequently, ex-vivo stimulation studies were performed in 15 healthy volunteers through the course of the four seasons of the year. PBMC were isolated and stimulated with Toll-like receptor (TLR)-2 and TLR-4 ligands Pam3Cys and LPS, respectively. Circulating concentrations of 25(OH)D(3) and 1,25(OH)(2) D(3) were higher during summer (P<0·05) and a down-regulation of TLR-4-mediated IL-1β, IL-6, TNF-α, interferon (IFN)-γ and IL-10 production in summer was observed compared to winter (P<0·05). The variation in cytokine response upon TLR-2 (Pam3Cys) stimulation was moderate throughout the four seasons. The repressed cytokine production during the summer months could be explained partly by the reduced cell-membrane expression of TLRs. Physiological variation in vitamin D(3) status through the four seasons of the year can lead to alteration in the innate immune responses. Elevated vitamin D(3) level in vivo is associated with down-regulation of cytokine response through diminished surface expression of pattern recognition receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcitriol / blood*
  • Calcitriol / pharmacology
  • Cysteine / analogs & derivatives
  • Cysteine / pharmacology
  • Cytokines / analysis
  • Cytokines / blood*
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / blood
  • Interleukin-1beta / analysis
  • Interleukin-1beta / blood
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Seasons*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood
  • Vitamins / blood
  • Vitamins / pharmacology


  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Vitamins
  • Interferon-gamma
  • tripalmitoyl cysteine
  • Calcitriol
  • Cysteine