Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations

Marianna Miliaraki; Panagiotis Briassoulis; Stavroula Ilia; Kalliopi Michalakakou; Theodoros Karakonstantakis; Aikaterini Polonifi; Kalliopi Bastaki; Efrossini Briassouli; Konstantinos Vardas; Aikaterini Pistiki; Maria Theodorakopoulou; Theonymfi Tavladaki; Anna-Maria Spanaki; Eumorfia Kondili; Helen Dimitriou; Maria Venihaki; Sotirios Tsiodras; Dimitrios Georgopoulos; Marina Mantzourani; Serafeim Nanas; Apostolos Armaganidis; George L Daikos; Ioannis Papassotiriou; George Briassoulis

doi:10.3390/antiox11020231

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations

Antioxidants (Basel). 2022 Jan 25;11(2):231. doi: 10.3390/antiox11020231.

Authors

Marianna Miliaraki¹, Panagiotis Briassoulis¹, Stavroula Ilia¹, Kalliopi Michalakakou², Theodoros Karakonstantakis², Aikaterini Polonifi³, Kalliopi Bastaki¹, Efrossini Briassouli³, Konstantinos Vardas⁴, Aikaterini Pistiki⁵, Maria Theodorakopoulou⁶, Theonymfi Tavladaki¹, Anna-Maria Spanaki¹, Eumorfia Kondili⁷, Helen Dimitriou⁸, Maria Venihaki⁹, Sotirios Tsiodras⁵, Dimitrios Georgopoulos⁷, Marina Mantzourani³, Serafeim Nanas⁴, Apostolos Armaganidis⁶, George L Daikos³, Ioannis Papassotiriou², George Briassoulis¹

Affiliations

¹ Pediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, Greece.
² Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, 11527 Athens, Greece.
³ First Department of Internal Medicine-Propaedeutic, National and Kapodistrian University of Athens, 11527 Athens, Greece.
⁴ First Critical Care Department, Evangelismos University Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece.
⁵ 4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece.
⁶ 2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
⁷ Department of Intensive Care Medicine, University Hospital of Heraklion and Medical School, University of Crete, 71110 Heraklion, Greece.
⁸ Laboratory of Child Health, School of Medicine, University of Crete, 71003 Heraklion, Greece.
⁹ Department of Clinical Chemistry, School of Medicine, University of Crete, 71003 Heraklion, Greece.

Abstract

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 AUC_TOS/TAC (0.96 (95% CI = 0.93-0.99)) was higher than AUC_TAC (z = 20, p < 0.001) or AUC_TOS (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.

Keywords: TAC; TOS; antioxidant status; apoptosis; heat shock proteins; innate immunity; interleukins; oxidative stress.

Grants and funding

KA 4975/Special Account for Research Funds of the University of 356 Crete