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

Abstract

Background Vitamin D plays an important role in inflammatory responses after antigen exposure. Interleukin-23 (Il-23) promotes Il-17-dependent inflammation during Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection. We aimed to compare the ability of calcitriol and cholecalciferol to modulate the inflammatory response of the CF airways infected with P. aeruginosa. Methods This was a randomized, placebo-controlled, double-blind, cross-over trial. Twenty-three patients with CF (aged 6–19), chronically infected by P. aeruginosa were randomly assigned to: calcitriol group receiving 1,25(OH) 2 D 0,5 mcg daily or cholecalciferol group receiving cholecalciferol 1000 IU daily for three months. The levels of Il-23 and Il-17A in the exhaled breath concentrate (EBC) were measured. Calcium-phosphorus balance was also evaluated (serum concentration of calcium, phosphorus, 25OHD, parathormone (PTH) and calcium/creatinine ratio in urine). Data were analyzed using means of Stata/Special Edition, release 14.2. A level of P < 0.05 was considered statistically significant. Results The level of Il-17A in EBC significantly decreased in calcitriol group from 0,475 pg/mL (± SD 0,515 pg/mL) to 0,384 pg/mL (± SD 0,429 pg/mL) ( p = 0,008 ); there was no change in cholecalciferol group ( p = 0,074 ). The level of Il-23 in EBC did not significantly change in calcitriol group ( p = 0,086 ); there was significant decrease in cholecalciferol group from 8,90 pg/mL (± SD 4,07 pg/mL) to 7,33 pg/mL (± SD 3,88 pg/mL) ( p = 0,001 ). In calcitriol group serum phosphorus and PTH significantly decreased ( p = 0,021 and p = 0,019 respectively), the concentration of calcium significantly increased ( p = 0,001 ); there were no changes in cholecalciferol group . Conclusions Both analogs of vitamin D revealed their anti-inflammatory effect and reduced the level of Il-17A and Il-23 in the airway of CF patients with chronic P. aeruginosa infection. We observed improvement in calcium-phosphorus metabolism after supplementation with calcitriol, without adverse effects. It is recommended to use vitamin D in CF patients.

Vitamin D in COVID - 19: Dousing the fire or averting the storm? – A perspective from the Asia-Pacific

“…It suppresses the release of inflammatory cytokines and chemokines such as IL-2, tumor necrosis factor-α and interferon-γ, and thus suppresses responses mediated by T helper cell type 1 (Th1) [ 37 , 38 ]. This may help to reduce the cytokine storm that is noted in Covid-19 patients [ 39 ] and which is the pathophysiologic driver behind systemic inflammatory response syndrome and acute respiratory distress syndrome [ 40 , 41 ]. TLRs are also instrumental in activating adaptive immunity.…”

Auto-antibody evaluation in idiopathic interstitial pneumonia and worse survival of patients with Ro52/TRIM21auto-antibody

“…1, 25-dihydroxycholecalciferol calcitriol, [1,25(OH) 2 D 3 ] is activate form of vitamin D, and calcitriol inhibited IL-23/IL-17 in the airway of cystic fibrosis patients. ( 51 ) Furthermore, calcitriol prevented experimental lung fibrosis model in mice via inhibiting inflammation and accumulation of activated fibroblasts. ( 52 ) Thus, IL-23/IL-17 pathway possibly is involved in IP development, however our preliminary examination of the serum IL-17 concentration did not show apparent elevation of IL-17A in Ro52 positive patients.…”

Therapeutic approaches for SARS-CoV-2 infection

“…Vitamin D also regulates suppression of adaptive immune responses during viral infection via inhibiting T-cell proliferation (type I) resulting in reduced pro-inflammatory cytokines [145] , [146] . Further, it inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NFκβ) pathway [147] and also diverts the development of inflammatory T-helper (type 17) cells into anti-inflammatory regulatory T-cells (T-reg cell) which reduces the expression of pro-inflammatory cytokines such as IL-1, IL-6, IL-10, IL-12, IL-17, IL-23 and TNF-α [145] , [146] , [148] . Vitamin D has also been reported to downregulate the expression of ACE2 receptors [149] .…”