Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis

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.

Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study

“…7,28,32 When Toll-like receptors on macrophages bind bacterial wall lipopolysaccharide, 1-a-hydroxylase and VDR expression is upregulated, resulting in the local conversion of 25(OH)D to 1,25(OH) 2 D, which in turn increases the expression of bactericidal proteins, cathelicidin, and beta defensin. 14 Cathelicidin transcription is particularly dependent on sufficient circulating levels of 25(OH)D. 14,33 The findings of the present study are consistent with these biologic principles and other epidemiologic reports linking low serum 25(OH)D levels to increased risks of infection in the nondialysis population. 34,35 The present study makes an important contribution to the literature by demonstrating this association in the chronic dialysis population and provides another plausible mechanism for the well known impaired immunity in these patients.…”

RETRACTED ARTICLE: Evaluation of the Relationship Between Serum Vitamin D Level and Severity of Sepsis

“…The severity of an infection is negatively correlated to serum vitamin D concentrations. These findings proposed another important role for this vitamin in the progression of sepsis pathogenesis (11)(12)(13). The…”

Deficiency in 25-Hydroxyvitamin D and 30-Day Mortality in Patients With Severe Sepsis and Septic Shock

“…29,30 A study 31 of 80 patients who came to the emergency department because of suspected infection indicated that patients with serum levels of 25-hydroxyvitamin D less than 30 ng/mL had a higher incidence of severe sepsis within 24 hours than did patients with higher serum levels. Additionally, a recent retrospective cohort study 32 of more than 3000 patients indicated that risk for sepsis was 1.6-fold higher in critically ill patients with serum levels of 25-hydroxyvitamin D less than 15 ng/mL compared with patients in the cohort with 25-hydroxyvitamin D concentrations of 30 ng/mL or higher.…”