Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body’s first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed.

This study assesses the role of neutrophils in indomethacin-induced small bowel injury and determines the influence of intestinal pH on the magnitude of this injury. Rat jejunum was perfused via the lumen with buffer, and mucosal injury was assessed by blood-to-lumen clearance of 51Cr-EDTA and quantitative histology. Reduction in luminal pH from 7.4 to 6.0 in the presence of indomethacin (1.0 mg/ml) increased 51Cr-EDTA clearance from 2.0 +/- 0.1 to 6.5 +/- 0.3 microliter.min-1.g-1. Indomethacin caused a reduction in villus length, an increase in villus width, and an increase in lesion score. Depletion of neutrophils with antiserum largely prevented the increase in 51Cr-EDTA clearance and morphological changes. Intravenous indomethacin given at a dose to mimic therapeutic plasma levels (1 mg/kg iv) had no significant effect on 51Cr-EDTA clearance but caused similar morphological changes to those observed following intraluminal administration. The data suggest that neutrophils play a role in acute indomethacin injury and that the drug given intravenously can cause morphological changes without necessarily altering mucosal permeability to 51Cr-EDTA.