Treatment with 24 h–delayed normo- and hyperbaric oxygenation in severe sepsis induced by cecal ligation and puncture in rats

Abstract

BackgroundSeptic shock remains a leading cause of death worldwide. Hyperbaric oxygen treatment (HBO2) has been shown to alter the inflammatory response during sepsis and to reduce mortality. A therapeutic window of HBO2 treatment has been demonstrated experimentally, but optimal timing remains uncertain. We investigated the effects of 24 h delayed normobaric oxygen (NBO2) and HBO2 treatment on the endogenous production of the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10, and on mortality in rats with cecal ligation and puncture (CLP) induced sepsis.MethodFifty-five male Sprague-Dawley rats underwent CLP and were randomized to the following groups: 1) HBO2 2.5 bar absolute pressure (pabs); 2) NBO2 1.0 bar pabs; 3) Control (no-treatment), and they were individually monitored for 72 h with intermittent blood sampling.ResultsIL-6, TNF-α, and IL-10 were increased 24 h after the procedure, and IL-6 was significantly higher in non-survivors than in survivors. The level of IL-10 was significantly higher at hour 48 in the HBO2 group compared to control (p = 0.01), but this was not the case at other time points. No other significant differences in cytokine levels were found for any group comparisons. Delayed NBO2 and HBO2 treatment failed to change the mortality in the animals.ConclusionHigh levels of IL-6 in non-surviving animals with sepsis suggest that IL-6 is a potential biomarker. We found a significantly higher concentration of IL-10 in the HBO2 group at hour 48 vs. control animals. However, 24 h–delayed treatment with HBO2 did not change the levels of pro-inflammatory cytokines and survival, suggesting that earlier intervention may be required to obtain an anti-inflammatory effect.

Hyperbaric oxygen treatment is associated with a decrease in cytokine levels in patients with necrotizing soft‐tissue infection

“…HBO 2 treatment induces several immunomodulatory effects that may well explain the observed cytokine fluctuations before and after HBO 2 treatment. Studies of experimental sepsis have indicated that HBO 2 treatment exerts its antimicrobial effect by enhancement of IL‐10, which lowers IL‐6 and thereby reduces the overall mortality in HBO 2 ‐treated animals (Bærnthsen et al, 2017; Buras et al, 2006). However, we were unable to detect any fluctuations of IL‐10 after HBO 2 treatment, but this discrepancy may well be explained by our time of blood sampling immediately after treatment which does not respect the less rapid kinetics of IL‐10 (Khatri & Caligiuri, 1998).…”

“…IL-1β, a powerful proinflammatory cytokine primarily created by activated macrophages and monocytes, acts on a variety of immune cells including the endothelium, amplifying the inflammatory process by release of proinflammatory cytokines-such as IL-6-and reactive oxygen and nitrogen species (Schulte et al, 2013). In this context, it may be of importance to note, that both ICAM-1 and IL-6 are modified by HBO 2 treatment in experimental sepsis (Baernthsen et al, 2017;Buras et al, ,2000Buras et al, , , 2006Halbach et al, 2019). Some evidence indicates that G-CSF-a hematopoietic-cell growth factor-is involved in sepsis pathogenesis and has crucial functions on mature myeloid cells and the innate immune system during inflammation (Hamilton, 2008;Roberts & Roberts, 2005).…”

“…In this respect, it is important to note that HBO 2 treatment has been proposed to have regulatory effects on the expression of IL‐1β during infections (Lerche et al, 2017). Likewise, in experimental sepsis in rats HBO 2 treatment has shown to stimulate immune‐modulatory activities including IL‐10 modulation resulting in improved survival (Bærnthsen et al, 2017; Buras et al, 2006), but timing and dosage are essential factors for the overall outcome (Bærnthsen et al, 2017; Buras et al, 2006; Lerche et al, 2017).…”

“…The lack of clinical studies, the inconsistency in the use of HBO 2 treatment and the uncertainties surrounding the mechanisms of action all highlight the need for studies describing the potential effects of HBO 2 treatment in NSTI treatment. Of particular relevance is the question if HBO 2 treatment can induce immune‐modulatory effects in patients with NSTI as experimental studies have suggested (Bærnthsen et al, 2017; Buras et al, 2006; Lerche et al, 2017). Therefore, we aimed to evaluate the plasma levels of inflammatory cytokines in patients with NSTI during the first 3 days after admission.…”

Do Late Phase Hyperbaric and Normobaric Oxygen Therapies have Effect on Liver Damage? An Experimental Sepsis Model

“…Studies regarding HBO as adjuvant therapy in sepsis have also been performed in the past, and its beneficial effects have been reported [12,32]. The role of cellular oxidative damage in multiple organ dysfunction syndrome is well-known.…”