Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis

Abstract

Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

“…A recent study even reported that the secretion of the pro-inflammatory cytokine IFN γ-induced protein 10 (IP-10) was increased by vitamin D treatment in RV-infected healthy airway epithelial cells [39]. However, an interesting study by MCNALLY et al [30] showed that vitamin D receptor agonists decreased the release of pro-inflammatory cytokines, such as IL-8 and IL-6, by the CF airway epithelium in response to antigen challenge. The conflicting results could be due to different pathogen challenges (Pseudomonas aeruginosa versus RV) and due to the cell culture model used [28] (cell lines versus primary cells), which might result in different inflammatory responses.…”

“…Also, vitamin D has been reported to have anti-inflammatory effects in airway epithelial cells [4,30]. Thus, we studied whether vitamin D treatment reduced RV-induced cytokine production in CF cells.…”

Weekly cholecalciferol supplementation results in significant reductions in infection risk among the vitamin D deficient: results from the CIPRIS pilot RCT

“…Our hypothesis was that vitamin D enables the effective responsiveness of innate immune system pathways and thus improves the ability of the body to block the colonisation by pathogens [4,[25][26][27][28][29][30], so an effect of vitamin D on absolute infection risk was expected. Vitamin D also has the capacity to depress inflammatory immune pathways like IP-10 and IL-8 [31,32], enabling an effective but less inflammatory response. Thus, an effect on infection severity is expected from vitamin D sufficiency.…”

Vitamin D: Genetics and Genomic Effects

“…Given the associations with other obstructive in fl ammatory lung diseases and the recent report that 1,25(OH)D signi fi cantly reduces the pro-in fl ammatory response to antigen challenge in cystic fi brosis airway epithelial cells [ 99 ] , genetic studies of the vitamin D pathway related to lung outcomes in cystic fi brosis are warranted, but have not yet been performed. In a small case-control study, Roth et al [ 100 ] evaluated the association of the VDR FokI and TaqI polymorphisms with lower respiratory infection susceptibility in children, comparing 56 young children hospitalized with acute lower respiratory infection and 64 childhood controls.…”