Commentary
Vitamin D and the Magic Mountain: The Anti-Infectious Role of the Vitamin

https://doi.org/10.1016/j.jpeds.2010.02.002Get rights and content

Section snippets

Historical Context

Circumstances in the social and geographical features of Glasgow, Scotland, in the late 19th and early 20th centuries provide a window into the full scope of rickets, which was common in Europe and North America. Not only was the prevalence of rickets high,26 it was so common that it was actually difficult to find enough non-rachitic children to conduct clinical trials on the etiology of rickets in Glasgow.27 In 1908, >1000 osteotomies were performed on rachitic children at the Royal Hospital

Vitamin D as an Immune Modulator

In the past 15 years, we have sought mechanisms to account for the non-osseous effects of vitamin D. Vitamin D, particularly in its active form, 1,25(OH)2D, is appreciated as a secosteroid that functions as a gene transcription factor. After binding to a VDR, this complex is then translocated to an intranuclear site.6, 17 VDRs are found in >30 tissue types, including the heart, intestine, liver, kidney, lungs, and various immune cells, such as thymic and bone marrow T and B cells.6, 11, 17

Influence on Innate Immunity

Although 1,25(OH)2D action dampens the effects of activation of the acquired immune system relative to autoimmunity, this hormone has key actions that enhance the innate immune system.6, 17, 21, 33 The influence of vitamin D on innate immunity is dependent on tissue concentrations of 1,25(OH)2D and is regulated by 2 enzymes: the activating 25(OH)D 1α-hydroxylase (CYP27b1) and its catabolic counterpart, 25(OH)D 24-hydroxylase (CYP24).6 The entry of 25(OH)D, the main substrate for CYP27b1 and

Vitamin D Status and Implications for Infection

The role of vitamin D status in innate immunity helps explain some of long-held views on the role of sunlight in the clinical course of TB. Both clinical observations and epidemiologic studies exist that show that M tuberculosis is suppressed by sunlight exposure and by habitation at higher elevations.42 TB is more common in patients with rickets and vitamin D deficiency per se6, 22; it is also more prevalent in dark-skinned individuals whose melanin blocks out the UV wavelength necessary for

Conclusion

The risk of respiratory infections, including TB, influenza, pneumonia, and other upper and lower respiratory tract infections, is much greater in children with vitamin D deficiency (serum 25(OH)D <10 ng/mL). This inverse relationship between vitamin D status (low in winter and high in summer) and infection is what was found when rickets was epidemic. Recent experiments have shed light on the immune-enhancing properties of vitamin D, especially involving innate immunity and localized monocyte

First page preview

First page preview
Click to open first page preview

References (52)

  • M. Hewison et al.

    Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease

    J Steroid Biochem Mol Biol

    (2007)
  • A.R. Masten

    Good climate - an asset in the treatment of tuberculosis

    Chest

    (1937)
  • M. Pfleiderer et al.

    Cold-attenuated live influenza vaccines, a risk-benefit assessment

    Vaccine

    (2001)
  • L. Muhe et al.

    Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children

    Lancet

    (1997)
  • B. Dawson-Hughes et al.

    Estimates of optimal vitamin D status

    Osteoporos Int

    (2005)
  • A.A. Ginde et al.

    Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004

    Arch Intern Med

    (2009)
  • C.M. Gordon et al.

    Prevalence of vitamin D deficiency among healthy infants and toddlers

    Arch Pediatr Adolesc Med

    (2008)
  • M.F. Holick

    Vitamin D deficiency

    N Engl J Med

    (2007)
  • M. Misra et al.

    Vitamin D deficiency in children and its management: review of current knowledge and recommendations

    Pediatrics

    (2008)
  • K. Rajakumar

    Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective

    Pediatrics

    (2003)
  • A.J. Rovner et al.

    Hypovitaminosis D among healthy children in the United States: a review of the current evidence

    Arch Pediatr Adolesc Med

    (2008)
  • J.A. Taylor

    Defining vitamin D deficiency in infants and toddlers

    Arch Pediatr Adolesc Med

    (2008)
  • O. Torkildsen et al.

    Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis

    Arch Neurol

    (2008)
  • E.A. Park

    The etiology of rickets

    Physiol Rev

    (1923)
  • R. Bouillon et al.

    Vitamin D and human health: lessons from vitamin D receptor null mice

    Endocr Rev

    (2008)
  • G. Jones et al.

    Contemporary diagnosis and treatment of vitamin D-related disorders

    J Bone Miner Res

    (2007)
  • Cited by (96)

    • Nutritional and stress effects on immunologic function

      2020, Stiehm's Immune Deficiencies: Inborn Errors of Immunity
    • Vitamin D's role in health and disease: How does the present inform our understanding of the past?

      2018, International Journal of Paleopathology
      Citation Excerpt :

      The immune system has also been identified as a major target for non-classic actions of vitamin D, and the VDR and 1-α hydroxylase are expressed in many immune cell types, supporting the idea that low vitamin D status may affect the development of autoimmune diseases, infections, or inflammation. Within the immune system, 1,25(OH)2D is typically considered to inhibit adaptive immune responses and to promote innate immunity (Bikle, 2009), generally stimulating antigen processing, phagocytosis, and the production of cytokines that encourage the elimination of foreign antigens and pathogens (Chesney, 2010; Hewison, 2012). Vitamin D modulates the phenotype and function of antigen presenting cells (Adorini, 2005), as well as shifting the balance of T cell actions toward a more regulatory response (Adams et al., 2007; White, 2008).

    • Calcium and vitamin D in human health: Hype or real?

      2018, Journal of Steroid Biochemistry and Molecular Biology
    • Vitamin D deficiency in mothers, neonates and children

      2018, Journal of Steroid Biochemistry and Molecular Biology
      Citation Excerpt :

      There are a number of possible pathways that suggest a relationship between maternal vitamin D level and infant’s predisposition to infections. Vitamin D has a direct role in the production of antimicrobial peptides such as cathelicidin which may help prevent infection during pregnancy and/or early childhood [26,27] (Table 3). One recent published study proved an association between early onset neonatal sepsis and low maternal vitamin D levels in term infants [28].

    View all citing articles on Scopus

    The author declares no conflicts of interest.

    View full text