Vitamin D treatment modulates immune activation in cystic fibrosis

Abstract

Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation. Three months of vitamin D treatment were followed by two washout months. Vitamin D status at baseline was correlated negatively with haptoglobin, erythrocyte sedimentation rate and immunoglobulin A concentration. Total vitamin D dose per kg bodyweight correlated with the down-modulation of the co-stimulatory receptor CD86 on mDCs. Vitamin D treatment was associated with reduced CD279 (PD-1) expression on CD4 and CD8 T cells, as well as decreased frequency of CD8 T cells co-expressing the activation markers CD38 and human leucocyte antigen D-related (HLA-DR) in a dose-dependent manner. There was a trend towards decreased mucosal-associated invariant T cells (MAIT) cell frequency in patients receiving vitamin D and free serum 25-hydroxyvitamin D (free-s25OHD) correlated positively with CD38 expression by these cells. At the end of intervention, the change in free-s25OHD was correlated negatively with the change in CD279 (PD-1) expression on MAIT cells. Collectively, these data indicate that vitamin D has robust pleiotropic immunomodulatory effects in CF. Larger studies are needed to explore the immunomodulatory treatment potential of vitamin D in CF in more detail.

Vitamin D inhibits pro-inflammatory cytokines in the airways of cystic fibrosis patients infected by Pseudomonas aeruginosa- pilot study

“…The most trails which have shown reduction of inflammation and improved lung function in CF patient have administered at least a double dose (above 2000 IU) of cholecalciferol [25, 26]. Pincikova et al [27]. randomized CF patients to receive 35,000–50,000 IU vitamin D per week for three months and observed that this supplementation has pleiotropic immunomodulatory effects in CF in a dose-dependent manner.…”

Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells

“…Plasma levels of IL-1b, IL-6, IL-8, tumor necrosis factor, transforming growth factor-b, IL-10, IL-17, interferonl-inducible protein 10, monocyte chemoattractant protein-1, IL-7, IL-18, IgG, IgM, IgA, and IgE were within the normal range (not shown). Frequencies of natural killer cells, B cells, T cells, regulatory T cells, and invariant natural killer T (iNKT) cells were normal (Table 1) 3 ; however, mucosal-associated invariant T (MAIT) cells were strikingly undetectable on three different occasions (Table 1 and Fig 1A). 3 In contrast, normal MAIT cell levels were detected in healthy donors as well as in matched patients with CF ( Fig 1A).…”

“…Frequencies of natural killer cells, B cells, T cells, regulatory T cells, and invariant natural killer T (iNKT) cells were normal (Table 1) 3 ; however, mucosal-associated invariant T (MAIT) cells were strikingly undetectable on three different occasions (Table 1 and Fig 1A). 3 In contrast, normal MAIT cell levels were detected in healthy donors as well as in matched patients with CF ( Fig 1A). The patient's father and sister had normal levels, whereas his mother had one log lower than normal MAIT cell frequency ( Fig 1B).…”

Acylation derivatization based LC-MS analysis of 25-hydroxyvitamin D from finger-prick blood

“…The specific mechanism was still not well understood. Nonetheless, as vitamin D could lower plasma erythropoietin levels, we hypothesized that the breakdown of fetal erythrocytes might be decelerated through this route so that the negative correlation between 25(OH)D and IBIL/TBIL was observed (23). On the other hand, evidence had shown that normal newborn erythrocytes were relatively sensitive to oxidative damage (24).…”