Attenuation of ventilator-induced lung injury through suppressing the pro-inflammatory signaling pathways: A review on preclinical studies

Abstract

Mechanical ventilation (MV) is a relatively common medical intervention in ICU patients. The main side effect of MV is the so-called "ventilator-induced lung injury" (VILI). The pathogenesis of VILI is not completely understood; however, it has been reported that MV might be associated with up-regulation of various inflammatory mediators within the lung tissue and that these mediators might act as pathogenic factors in lung tissue injury. One potential mechanism for the generation of inflammatory mediators is through the release of endogenous molecules known as damage associated molecular patterns (DAMPs). These molecules are released from injured tissues and can bind to pattern recognition receptors (PRRs). PRR activation generally leads to the production and release of inflammation-related molecules including innate immune cytokines and chemokines. It has been suggested that blocking DAMP/PRR signaling pathways might diminish the progression of VILI. Herein, we review the latest findings with regard to the effects of DAMP/PRRs and their blockade, as well as the potential therapeutic targets and future research directions in VILI. Results of studies performed on human samples, animal models of disease, as well as relevant in vitro systems will be discussed.

Keywords: Biotrauma; Damage associated molecular pattern (DAMP); Pattern recognition receptor (PRR); Signaling pathway; Ventilator-induced lung injury (VILI).