Immunomodulation by extracorporeal ozone-based bactericide system in porcine Pseudomonas aeruginosa septic shock

Abstract

Abstract Sepsis is associated with substantial mortality rates. Traditional treatment strategies often fail to address the underlying dysregulation in immune response, necessitating novel therapeutic approaches. Ozone (O3) is an inorganic molecule with no evident function in the body. We investigated the properties of ozone, using a system of extracorporeal ozone blood treatment in Pseudomonas aeruginosa septic shock. We hypothesized that extracorporeal ozonation would decrease bacteria in blood, have immunomodulating properties, and improve organ function. In this 4-h sepsis model swine were allocated to P. aeruginosa (PA-103, ATCC 29260, CCUG31589) infusion and ozone treatment (n = 7) or P. aeruginosa infusion and no ozone treatment (n = 6). Bacteria were infused in a peripheral vein. Mean (SD) duration of ozone treatment was 134 (67) min. A single pass through the system decreased viable P. aeruginosa by 53%, mean 2193 to 1023 colony forming units/mL, mean of differences -1170 (95% CI − 1689 to − 651, P < 0.0001). No difference in viable bacterial concentration was detected in peripheral venous blood between groups (P = 0.68). IL-1β, IL-4, IL-6, IL-8 and IFN-γ decreased by ozonation. Classical and alternative complement pathways were not affected. Blood hemoglobin, hematocrit and noradrenaline doses decreased in the treatment group. Breathing frequency and pulmonary peak airway pressure decreased in the ozone treatment group. Median survival in ozone treatment was 134 min and no treatment 159 min, with no statistical difference. Extracorporeal ozone blood treatment modulated the immune response in P. aeruginosa septic shock, which decreased mostly proinflammatory cytokines and was associated with indications of decreased vascular permeability and improved lung function and warrants further investigation for potential use in clinical settings.