Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

Abstract

Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS). Maresin 1 (Mar1) is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP) with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS) and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb) pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain–Fas‐associated death domain interaction

“…Resolution mediators LXA 4 and MaR1 levels were higher in the peritoneal fluid in sevoflurane group, suggesting that mice exposed to sevoflurane demonstrated earlier resolution from inflammation. LXA 4 facilitated peritoneal neutrophil phagocytic activity without apoptosis in CLP model (63), and MaR1 attenuated proinflammatory mediators and organ injury (64,65), which is in line with our survival result. The studies from Herrmann and us are very promising to suggest sevoflurane as a preferred anesthetic drug in the setting of sepsis.…”

Atrial Arrhythmias in a Patient Presenting With Coronavirus Disease-2019 (COVID-19) Infection

“…20 Arrhythmias are complex and multifactorial in a COVID-19 patient and may result from metabolic derangements, hypoxia, acidosis, intravascular volume imbalances, neurohormonal, and catecholaminergic stress. 21,22 Sepsis is characterized by a systemic milieu involving inflammatory cytokines and autonomic dysfunction. 23 This maladaptive pathophysiology is a significant trigger for the development of AF, as was illustrated in this patient.…”

Maresin 1, a Proresolving Lipid Mediator, Ameliorates Liver Ischemia-Reperfusion Injury and Stimulates Hepatocyte Proliferation in Sprague-Dawley Rats

“…TNF-α acts as a pleiotropic molecule, because in the absence of Akt and NF-κB activation signaling, TNF-α mediates hepatocyte apoptosis and liver failure in mice [30]. A bulk of studies have highlighted the relation of MaR1 and the decrease of TNF-α, IL-6, and IL-1β [31][32][33][34], but they did not analyze the proliferatory potential of MaR1. Paradoxically, we found a decrease of TNF-α, but an increase in IL-6 at 3 h of perfusion, for that reason, we hypothesized that there was a prime event early in reperfusion (less than 1 h).…”