Oxidative stress is considered pivotal in the pathophysiology of
sepsis.
Oxidants modulate
heat shock proteins (Hsp),
interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an
oxidant/
antioxidant imbalance is an independent
sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with
sepsis (n = 145), compared to non-infectious
critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total
antioxidant capacity (TAC) were measured by photometric testing.
IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected
antioxidant biomolecules (Ζn,
glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic
survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious
critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores,
procalcitonin,
IL-6, -10, -27, IFN-γ, Hsp72, Hsp90,
survivin protein, and
survivin isoforms -2B, -ΔΕx3, -WT (p < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only
sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p < 0.001). The AUCTOS/TAC (0.96 (95% CI = 0.93-0.99)) was higher than AUCTAC (z = 20, p < 0.001) or AUCTOS (z = 3.1, p = 0.002) in distinguishing
sepsis. TOS/TAC, TOS,
survivin isoforms -WT and -2B, Hsp90,
IL-6,
survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01).
Oxidant/
antioxidant status is impaired in septic compared to
critically ill patients with
trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.