Oxidative Stress in Critically Ill Ventilated Adults: Effects of Vitamin D(3) and Associations with Alveolar Macrophage Function

BACKGROUND: Disruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: 1) characterize the plasma and alveolar thiol/disulfide redox pools, 2) examine their associations with alveolar macrophage phagocytosis, and 3) determine the effect of high dose vitamin D(3) on plasma thiol/disulfide redox. METHODS: Subjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D(3) or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14. RESULTS: Baseline plasma Cys was inversely associated with alveolar PI (ρ = −0.69, P=0.003), and E(h)CySS was positively associated with PI (ρ = 0.61, P=0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in E(h)GSSG (P<0.01 for both), with no difference by treatment group. Vitamin D(3) decreased oxidized plasma GSSG to a more normal state (P for group × time=0.009). CONCLUSIONS: Oxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D(3) decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.