Abstract
BackgroundVitamin D insufficiency is common in hospitalized patients. Recent evidence suggests that vitamin D may enhance the innate immune response by induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced by macrophages and neutrophils. Thus, the relationship between vitamin D status and LL-37 production may be of importance for host immunity, but little data is available on this subject, especially in the setting of human sepsis syndrome and other critical illness.MethodsPlasma concentrations of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (DBP) and LL-37 in critically ill adult subjects admitted to intensive care units (ICUs) with sepsis and without sepsis were compared to healthy controls.ResultsCritically ill subjects had significantly lower plasma 25(OH)D concentrations compared to healthy controls. Mean plasma LL-37 levels were significantly lower in critically ill subjects compared to healthy controls. Vitamin D binding protein levels in plasma were significantly lower in critically ill subjects with sepsis compared to critically ill subjects without sepsis. There was a significant positive association between circulating 25(OH)D and LL-37 levels.ConclusionThis study demonstrates an association between critical illness and lower 25(OH)D and DBP levels in critically ill patients as compared to healthy controls. It also establishes a positive association between vitamin D status and plasma LL-37, which suggests that systemic LL-37 levels may be regulated by vitamin D status. Optimal vitamin D status may be important for innate immunity especially in the setting of sepsis. Further invention studies to examine this association are warranted.
Highlights
Vitamin D is a pro-hormone important for serum calcium and phosphorus homeostasis for proper neuromuscular function and optimal skeletal health
We performed a cross-sectional study of vitamin D status including plasma levels of 25(OH)D and vitamin D binding protein (DBP) and their relationship to systemic LL-37 levels in a group of critically ill patients including those with and without sepsis
Samples were taken from three patient populations: Group 1 consisted of critically ill subjects in the intensive care unit (ICU) patients diagnosed with sepsis (as defined by the American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) consensus panel in 2001 [15]; Group 2 consisted of intensive care units (ICUs) subjects without the diagnoses of sepsis, and Group 3 consisted of 21 healthy non-hospitalized controls
Summary
Vitamin D is a pro-hormone important for serum calcium and phosphorus homeostasis for proper neuromuscular function and optimal skeletal health. Cells of the innate and adaptive immune system including macrophages, lymphocytes and dendritic cells express the vitamin D receptor (VDR) and respond to stimulation by 1,25(OH)2D [2,3]. The addition of 25(OH)D to the media up-regulated production of LL-37 and restored effective killing of M. tb, suggesting that vitamin D has an important role in the production of anti-microbial peptides important for innate immunity [3]. Recent evidence suggests that vitamin D may enhance the innate immune response by induction of cathelicidin (LL-37), an endogenous antimicrobial peptide produced by macrophages and neutrophils. The relationship between vitamin D status and LL-37 production may be of importance for host immunity, but little data is available on this subject, especially in the setting of human sepsis syndrome and other critical illness
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