Linking lung function and inflammatory responses in ventilator-induced lung injury

Abstract

Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

Hydrogen-rich saline ameliorates lung injury associated with cecal ligation and puncture-induced sepsis in rats

“…Previous studies have showed that hydrogen has a potential anti-inflammatory effect (Kajiya et al, 2009;Gharib et al, 2001). TNF-α, IL-1β and IL-6 are potent proinflammatory cytokines that play a role in the initiation and amplification of inflammatory responses during ALI (Cannizzaro et al, 2010). Inhibiting the overproduction of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 promotes the lessening of pulmonary injury in CLP-induced ALI model (Bhatia and Moochhala, 2004).…”

Systemic Inflammatory Response During Lung Recruitment Maneuvers in a Newborn Animal Model

“…[29] Chiumello et al [30] have reported an increase in cytokine concentrations in a group ventilated with high VT and zero PEEP. It has been suggested that considerably high VT may produce a similar degree of alveolar overdistension to that observed regionally in acute respiratory distress syndrome patients receiving much lower VT. [31] Therefore, in our study, the elevation of IL-6, and perhaps of IL-8 and IL-1β, could have been driven by high VT. A mouse model of ventilator-induced lung injury has shown that high-VT ventilation without preceding lung injury up-regulates intrapulmonary cytokines TNF-α. [32] TNF-α appears to be involved in the pathogenesis of both ventilatorinduced lung injury and multiorgan dysfunction syndrome.…”

“…[11,31] Moreover, the RM in our study was applied for a much longer period than what has been normally Vol-2 Issue-1 SIFT DESK used in other published animal models to assess the effects of this ventilatory strategy more accurately.…”

Effect of invariant natural killer T cells with IL-5 and activated IL-6 receptor in ventilator-associated lung injury in mice

“…Inflammatory cytokines such as IL-1β, IL-6, and TNF-α, detected in BALF, have been reported to be associated with the development of VALI [2,4,9]. Endotracheal instillation of anti-TNF-α antibody or lack of p55 TNF-α receptor signaling in mice has been reported to be associated with attenuation of VALI [16,39].…”

“…The pathogenesis of VALI is complex, involving factors including barotrauma, volutrauma, atelectasis, and biotrauma [9][10][11]. Some studies on animal models of VALI have shown that MV induces the release of proinflammatory cytokines/chemokines in the lung tissue, followed by accumulation of innate inflammatory leukocytes, such as neutrophils and macrophages [6].…”