The effects of vitamin D on acute viral respiratory infections: A rapid review
ADVANCES IN INTEGRATIVE MEDICINE
Authors: Bradley, Ryan; Schloss, Janet; Brown, Danielle; Celis, Deisy; Finnell, John; Hedo, Rita; Honcharov, Vladyslav; Pantuso, Traci; Pena, Hilda; Lauche, Romy; Steel, Amie
Brief overview: Current evidence suggests vitamin D replacement may reduce risk for acute respiratory tract infections (ARTI) in people with deficiency or insufficiency, although the effects of supplementation on incidence and severity of ARTI in the general population remain unknown. Oral vitamin D supplemzentation taken at routine doses appears to be generally safe and well tolerated. Verdict: Current experimental evidence remains inconclusive regarding the effects of vitamin D supplementation in the general population for the prevention and treatment of acute respiratory tract infections (ARTI). There is also insufficient evidence to draw conclusions regarding the impact of vitamin D supplementation on the severity or duration of ARTI, nor on outcomes related to lung injury or hospitalization from ARTI. Based on this rapid review, sources of significant heterogeneity in published clinical trials include: differences study populations, inconsistent assessment of serum status at baseline, dosing variability, varying routes of administration, and/or inconsistent definitions of outcome measures. Experimental evidence and observations in large cohorts are generally consistent that vitamin D deficiency (<50 nmol/L [<20 ng/mL]) and insufficiency (<75 nmol/L [<30 ng/mL]) of serum 25-hydroxycholecalciferol (25-OHD) concentration is associated with increased risk of ARTI, and supplementation for those with deficiency/insufficiency may lead to clinically meaningful reductions in the incidence of ARTI. In this rapid review, vitamin D was primarily administered as oral supplementation, and findings suggested significant differences in daily oral dosing compared to periodic bolus dosing. Based on the available experimental evidence, vitamin D supplementation appears to have a high margin of safety with very few adverse events reported in children or adults from a variety of dosing strategies. Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. The available mechanistic evidence related to immunological requirements for adequate vitamin D, the availability of observational and experimental evidence suggestive of clinically meaningful benefits (especially in deficient/insufficient participants), and the high margin of safety, should make vitamin D a high priority for additional clinical research during the current COVID-19 pandemic. (C) 2020 Published by Elsevier Ltd.
Tofacitinib restores the balance of gamma delta Treg/gamma delta T17 cells in rheumatoid arthritis by inhibiting the NLRP3 inflammasome
Authors: Yang, Xinyu; Zhan, Ning; Jin, Yang; Ling, Hanzhi; Xiao, Chipeng; Xie, Zhen; Zhong, Hao; Yu, Xinxin; Tang, Runhua; Ma, Jinglan; Guan, Jubo; Yin, Guoyu; Wu, Gan; Lu, Liangjing; Wang, Jianguang
Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (gamma delta Treg)/gamma delta T17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, gamma delta Treg/gamma delta T17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp3(-/-) mice were introduced to assess the influence of NLRP3 on.dT17 cell activation in RA. Results: TOF treatment decreased levels of gamma delta T17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the gamma delta Treg/gamma delta T17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1 beta via downregulation of NLRP3. Furthermore, experiments using Nlrp3(-/-) mice verified that the NLRP3 inflammasome mediated the effect of TOF on gamma delta T17 cell activation. Conclusions: Recovery of gamma delta Treg/gamma delta T17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated gamma delta T17 cell activation.