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

Abstract

Background: Vitamin 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.

Methods: Plasma 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.

Results: Critically 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.

Conclusion: This 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.

Figure 1

Vitamin D status in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects. Plasma 25-hydroxyvitamin D levels in critically ill subjects with sepsis (hatched bar) and in critically ill control subjects without sepsis (dark bar) were significantly lower than healthy controls (white bar) (ANOVA, p < 0.0001). 25-hydroxyvitamin D concentrations were adjusted for race. ‡ p < 0.001, critically ill sepsis subjects compared to healthy controls. # p < 0.01, critically ill control subjects compared to healthy controls.

Figure 2

Plasma vitamin D binding protein in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects. Plasma vitamin D binding protein concentrations were significantly lower in critically ill subjects with sepsis (hatched bar) compared to critically ill control subjects (dark bar) (white bar) (ANOVA, p = 0.014). † p = < 0.05, critically ill sepsis subjects compared to critically ill control subjects.

Figure 3

Anti-microbial peptide cathelicidin (LL-37) in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects. Plasma LL-37 levels were significantly lower in the two critical ill groups (with sepsis, hatched bar and without sepsis, dark bar) compared to the healthy controls subjects (white bar) (ANOVA, p= 0.002). There was no statistically significant difference between LL-37 levels in the two critically ill groups. ‡ p < 0.001, critically ill sepsis subjects compared to healthy controls. # p < 0.001, critically ill control subjects compared to healthy controls.

Figure 4

Relationship between plasma 25-hydroxyvitamin D and cathelicidin (LL-37) in critically ill subjects with sepsis, critically ill subjects without sepsis and healthy subjects. The was a positive relationship between plasma 25-hydroxyvitamin D (25(OH)D) and systemic LL-37 levels in all three subject groups (critically ill subjects with sepsis, critically ill without sepsis and healthy controls). This remained significant after adjustment for differences in race and patient population (R² = 0.21, P = 0.05).