Physicians' Academy for Cardiovascular Education

Vitamin D deficiency associated with proinflammatory status in elderly hypertensives

Literature - Laird et al., J Clin Endocrinol Metab 2014 - J Clin Endocrinol Metab 2014 Online February 25 2014

 

Vitamin D deficiency is associated with inflammation in older Irish adults

 
Laird E, McNulty H, Ward M
 J Clin Endocrinol Metab 2014. Online February 25 2014
 

Background

Although most known for its role in calcium regulation in bone metabolism, vitamin D is now recognised to have broader functions, including effects on immune regulation [1,2]. Because of this, ensuring sufficient vitamin D status in humans may help to optimise immune function, but many individuals worldwide are estimated to have deficient vitamin D levels [3,4]. Insufficient vitamin D status may lead to impaired immune function, with an increased vulnerability to proinflammatory state [5].
In vitro studies have shown that vitamin D can decrease concentrations of inflammatory cytokines like TNFα and IL-6, while increasing secretion of the anti-inflammatory cytokine IL-10 [6]. Other studies indicated that vitamin D shifts the immune response from an inflammatory (T-helper cell 1: TH-1) to an anti-inflammatory (TH-2) profile [7,8], but human studies have reported conflicting results.
This study examined the association of vitamin D status with immune markers of inflammation within an exclusively elderly population cohort, since they are at an increased risk of both insufficient and deficient vitamin D status, in the Trinity Ulster Department of Agriculture (TUDA) aging cohort. Data of 957 individuals with hypertension but otherwise healthy were included in this study.
 

Main results

  • A seasonal variation in 25(OH)D concentration was observed, with highest median concentrations of this vitamin D metabolite in summer (55.3 nmol/L, SD: 28.0), and the lowest in spring (38.6 nmol/L, SD 21.3). IL-10 also showed a significant seasonal variation, while no such effect of seasonality was seen for IL-6, CRP or TNFα.
  • With increasing vitamin D status, a decrease was seen in the concentration of IL-6, CRP and the ratios of IL-6 to IL-10 and CRP to IL-10, after adjustment for age, sex and BMI.
    In the group with sufficient vitamin D (>75 nmol/L), there were significantly fewer individuals with an IL-6 to IL-10 cytokine ratio >2:1, as compared to in those with insufficient and deficient (<25 nmol/L) vitamin D status (P=0.029 and P<0.001 respectively). Participants deficient for vitamin D were more likely to have an IL-6 to IL-10 ratio>2:1 than those with a sufficient vitamin D status.
  • Significant negative correlations were observed between serum 25(OH)D and IL-6, CRP, and the IL-6 to IL-10 ratio, and the CRP to IL-10 ratio, after adjustment for age, sex, BMI, smoking and presence of inflammatory conditions.
  • No significant correlation was seen between IL-10, TNFα and 25(OH)D concentrations.
  • Removal of patients with known inflammatory disease did not significantly alter the findings.
 

Conclusion

Hypertensive elderly patients showed significant negative associations between vitamin D and the pro-inflammatory markers IL-6 and CRP. A deficient vitamin D status was associated with a more proinflammatory profile (determined by IL-6 to IL-10 ratio). This suggests that insufficient vitamin D status may affect the inflammatory response, although a causal relationship cannot be concluded from these observational data. In light of published associations of the IL-6 to IL-10 ratio with cardiovascular disease, the capacity of vitamin D status to optimise immune function requires further exploration.
 
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References

1. Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D3 analogs as immunomodulatory agents. Trends Mol Med. 2002; 8:174–179.
2. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81:353–373.
3. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S–1086S.
4. van Schoor NM,Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25(4):671–680.
5. Ponsonby AL, McMichael A, Van-Der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological research. Toxicology. 2002;181–182:71–78.
6. Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J. 2001;15:2579–2585.

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