Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

Abstract

Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.

Association of polymorphisms in the vitamin D receptor gene with severity of hand, foot, and mouth disease caused by enterovirus 71

“…Vitamin D is a member of an important group of immunomodulators that regulate the growth, differentiation and function of various immune cells; affect the secretion of cytokines and antimicrobial peptides; and play an important role in regulation of innate and adaptive immunity as well as the inflammatory cascade . Vitamin D shifts the balance between proinflammatory and anti‐inflammatory processes toward an anti‐inflammatory phenotype, allowing the vitamin to control inflammatory bursts …”

“…[26][27][28] Vitamin D shifts the balance between proinflammatory and anti-inflammatory processes toward an anti-inflammatory phenotype, allowing the vitamin to control inflammatory bursts. 29 Numerous studies have linked vitamin D deficiency with the development of respiratory tract infections, diabetes, asthma, and autoimmune diseases in children. 11,3034 Neonates with low vitamin D levels are at significantly higher risk of developing acute lower respiratory tract infection than normal neonates, 31 critical HFMD patients than in healthy children, 35 which links the vitamin to HFMD pathogenesis.…”

The influence of vitamin D supplementation on local and systemic inflammatory markers in periodontitis patients: A pilot study

“…Among the immunomodulatory functions of vitamin D are its ability to shift the immune response toward an anti‐inflammatory response (Hoe et al, ). Albeit effective in treating periodontal disease, active periodontal therapy such as SRP results in transient bacteremia and entry of periodontal pathogens into the bloodstream.…”

“…Among the immunomodulatory functions of vitamin D are its ability to shift the immune response toward an anti-inflammatory response (Hoe et al, 2016).…”

Frailty and the immune system

“…Recent research efforts have explored the immunomodulatory effects of vitamin D and its potential use in the treatment of inflammatory diseases (94)(95)(96)(97) . The anti-inflammatory effect of vitamin D on human immune cells is well documented, with reduced production of pro-inflammatory cytokines (98,99) . With No substantial body of research supports other pharmacological treatments for frailty.…”