Relationship Between Vitamin D Status and Plasma Aminothiol Redox in Critically Ill Children

Abstract

BackgroundCritically ill populations incur high levels of oxidative stress. Vitamin D deficiency, which is common in children presenting to the pediatric intensive care unit (PICU), has been shown to correlate with plasma aminothiol redox imbalance, as well as systemic inflammation. The purpose of this study was to investigate the relationship between vitamin D status and plasma markers of aminothiol redox and inflammation in critically ill children.MethodsThis was a cross‐sectional study of n = 50 PICU patients. Blood was drawn within 24 hr of admission to the PICU. Plasma glutathione (GSH), glutathione disulfide (GSSG), cystine (Cys), and cysteine (CySS) were measured with high‐performance liquid chromatography, and their associated redox potentials determined (EhGSSG and Eh CySS, respectively). Plasma 25‐hydroxyvitamin D [25(OH)D] was measured using a chemiluminescent assay. Vitamin D insufficiency was defined as 25(OH)D levels < 30 ng/mL. Plasma markers of inflammation were assayed with a multiplex platform and ELISA.ResultsMean age (± SD) was 11.8 ± 5.2 yrs, and 56% of patients were male. 74% of patients had vitamin D insufficiency.. Proportionally fewer patients in the vitamin D insufficient group required mechanical ventilation (p=0.009). Plasma Cys and CySS did not differ by vitamin D status, although Eh CySS was lower (more reduced; p−=0.005) in the vitamin D sufficient group. Plasma GSH and GSSG were lower in the vitamin D sufficient group (p=0.017 and 0.011, respectively), with a trend towards lower EhGSSG in the vitamin D insufficient group (p=0.076). Plasma glutamine levels were lower in the vitamin D sufficient group (p=0.005). Plasma LL‐37 was higher in the vitamin D sufficient group (p=0.025), although there were no differences in other markers of inflammation. Adjustment for age, sex, race, weight, and ventilation status attenuated the difference in plasma Eh CySS (p=0.08). In linear regression analyses, serum 25(OH)D was inversely associated with plasma Eh CySS p=0.006), although adjustment for age, sex, race, weight, and ventilation status attenuated the relationship (p=0.09).ConclusionIn critically ill children, vitamin D sufficiency was associated with less oxidized plasma EhCySS, the redox state of the primary extracellular redox couple (Cys and CySS), and with higher plasma LL‐37, an indicator of innate immune function. Lower plasma GSH, GSSG, and glutamine in vitamin D sufficient patients may suggest vitamin D‐regulated mechanisms to preserve extracellular and/or the intracellular redox states during critical illness, although further study is needed.Support or Funding InformationThis study was supported by the Children's Healthcare of Atlanta Friends (grant number 38234), the National Institutes of Health (UL1 TR000454 and K01 DK102851), the Emory+Children's Statistical Core, and the Emory+Children's Biomarkers Core.