Resolution pharmacology and the treatment of infectious diseases.

Abstract

Inflammation is a physiological response composed by well-defined and overlapping events that can eliminate pathogens and reestablish homeostasis of tissues. Physiological systems have an elastic capacity to deal with numerous perturbations. Infection may lead to inflammation, tissue damage and disease as consequence of breakdown of tissue resilience. The resolutive phase is a sine qua non condition to achieve homeostasis after acute inflammation. Exuberant or chronic inflammation occurs in diverse infectious diseases. Pro-resolving molecules may be useful for the treatment of certain infections, as these molecules modulate the immune response and avoid the exacerbated/misplaced inflammation unleashed by microbes. Some pro-resolving molecules may also favour pathogen clearance, in addition to decreasing tissue damage. In this review, we discuss the endogenous role and the therapeutic potential of the most relevant pro-resolving molecules in the context of bacterial and viral infections.

Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice

“…Of note, Ang-(1-7) inhibits the phosphorylation of JAK/STAT proteins [39], which are essential regulators of local and systemic response to viral infections [40]. Indeed, JAK inhibitors such as baricitinib has antiviral properties against SARS-CoV-2 infection [41] suggesting that adjunctive anti-viral and anti-in ammatory/pro-resolving based strategies as potential therapies in the settings of infectious diseases [11,12]. Whether Ang-(1-7) is regulating the JAK/STAT pathway and contributing for the observed effect in viral load remain to be investigated.…”

“…RAS activation results in the production of angiotensin II, which upon binding to AT1 receptor evoke effects as vasoconstriction, in ammation, and oxidative stress [10]. Conversely, angiotensin-converting enzyme (ACE) 2 counteracts these effects by degrading angiotensin II into Ang-(1-7), which, upon activation of the MAS receptor, elicits anti-in ammatory, antioxidative, vasodilatory, and pro-resolving responses [11,12,14,26]. Early in COVID-19 pandemic several reviews claimed a putative bene c effect of Ang-(1-7) [27,28,29], given the known actions of this peptide.…”

“…More speci cally, ACE-2 is a key enzyme for angiotensin-(1-7) [(Ang-(1-7)] production, a mediator involved in the RAS non-classical pathway [10] and possesses both anti-in ammatory and pro-resolving actions in the lungs [11]. The biological effects of Ang-(1-7) are mainly mediated by Mas receptor (MasR) and have been shown to antagonize the pro-in ammatory actions of Ang II [11,12]. RAS dysregulation has been linked to in ammatory response exacerbation and development of severe acute respiratory syndrome, seen during severe pulmonary infections [13], such as in uenza A virus (IAV) infection [14,15,16].…”