Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury

Hoegl, Sandra; Boost, Kim Alexander; Czerwonka, Holger; Dolfen, Andrea; Scheiermann, Patrick; Mühl, Heiko; Zwißler, Bernhard; Hofstetter, Christian

doi:10.1016/j.rmed.2008.09.020

Cited by 32 publications

(38 citation statements)

References 43 publications

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“…Inflammatory cells can modulate both extracellular matrix degradation and epithelial cell migration through different mechanisms (24): release of proteases that cleave collagen, gelatin, and elastin; modulation of inflammation toward an anti-inflammatory response; and by directly releasing defensins and other growth factors that directly stimulate epithelial cell migration and proliferation (27). Our study supports the existence of some of these phenomena during the repair phase after VILI, including the release of proteases (MMP-2), a decrease of collagen levels, and the restoration of IL-10, an anti-inflammatory cytokine with beneficial effects in VILI (2,20).…”

Section: Discussionsupporting

confidence: 72%

“…The mechanical stimulus induces a secondary biochemical response in which inflammation (37) and extracellular matrix remodeling (32) are key processes. Although different pharmacological approaches have demonstrated a reduction in VILI (2,20,29,31), they have not been translated into the clinical practice and also pose a risk of adverse events. For example, modulation of the immune response can lead to an increased incidence of infection.…”

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confidence: 99%

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Inflammation and matrix remodeling during repair of ventilator-induced lung injury

González-López¹,

Astudillo

García-Prieto

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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High-pressure ventilation triggers different inflammatory and matrix remodeling responses within the lung. Although some of them may cause injury, the involvement of these mediators in repair is largely unknown. To identify mechanisms of repair after ventilator-induced lung injury (VILI), mice were randomly assigned to baseline conditions (no ventilation), injury [90 min of high-pressure ventilation without positive end-expiratory pressure (PEEP)], repair (injury followed by 4 h of low-pressure ventilation with PEEP), and ventilated controls (low-pressure ventilation with PEEP for 90 and 330 min). Histological injury and lung permeability increased during injury, but were partially reverted in the repair group. This was accompanied by a proinflammatory response, together with increases in TNF-α and IFN-γ, which returned to baseline during repair, and a decrease in IL-10. However, macrophage inflammatory protein-2 (MIP-2) and matrix metalloproteinases (MMP)-2 and -9 increased after injury and persisted in being elevated during repair. Mortality in the repair phase was 50%. Survivors showed increased cell proliferation, lower levels of collagen, and higher levels of MIP-2 and MMP-2. Pan-MMP or specific MMP-2 inhibition (but not MIP-2, TNF-α, or IL-4 inhibition) delayed epithelial repair in an in vitro wound model using murine or human alveolar cells cultured in the presence of bronchoalveolar lavage fluid from mice during the repair phase or from patients with acute respiratory distress syndrome, respectively. Similarly, MMP inhibition with doxycycline impaired lung repair after VILI in vivo. In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and acute respiratory distress syndrome.

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Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Inflammation and matrix remodeling during repair of ventilator-induced lung injury

González-López¹,

Astudillo

García-Prieto

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…29 Interestingly, inhaled IL-10 attenuates biotrauma and mortality in a ventilator-induced lung injury model in rats. 30 We did not observe an attenuation of proinflammatory cytokine levels, pulmonary ICAM-1 levels, or pulmonary neutrophil influx. A possible explanation for this could be that although IL-10 is known to attenuate inflammation, the acute phase response in our MV model is only a mild inflammatory response.…”

Section: Discussioncontrasting

confidence: 53%

Lidocaine increases the anti‐inflammatory cytokine IL‐10 following mechanical ventilation in healthy mice

Wal

Vaneker

Steegers

et al. 2014

Acta Anaesthesiol Scand

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Background: Mechanical ventilation (MV) induces an inflammatory response that may result in (acute) lung injury. Lidocaine, an amide local anesthetic, has anti-inflammatory properties in vitro and in vivo, possibly due to an attenuation of pro-inflammatory cytokines, intracellular adhesion molecule-1 (ICAM-1), and reduction of neutrophils influx. We hypothesized an attenuation of MV-induced inflammatory response with intravenously administered lidocaine. Methods: Lidocaine (Lido) (2, 4, and 8 mg/kg/h) was intravenously administered during 4 h of MV with a tidal volume of 8 ml/ kg, positive end expiratory pressure 1,5 cmH2O and FiO2 0.4. We used one ventilated control (CON) group receiving vehicle. After MV, mice were euthanized, and lungs and blood were immediately harvested, and cytokine levels and ICAM-1 levels were measured in plasma and lung homogenates. Pulmonary neutrophils influx was determined in LEDER-stained slices of lungs. Anesthetic need was determined by painful hind paw stimulation. Results: Lidocaine-treated animals (Lido 2, 4 and 8 mg/kg/h) showed higher interleukin (IL)-10 plasma levels compared to control animals. Lidocaine treatment with 8 mg/kg/h (Lido 8) resulted in higher IL-10 in lung homogenates. No differences were observed in pro-inflammatory cytokines, ICAM-1, and pulmonary influx between the different ventilated groups. Conclusions: Intravenously administered lidocaine increases levels of plasma IL-10 with infusion from 2, 4, and 8 mg/kg/h and pulmonary levels of IL-10 with 8 mg/kg/h in a murine mechanical ventilation model. Intravenously administered lidocaine appears to reduce anesthetic need in mice.

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“…IL-10, an activating factor for B lymphocytes, exerts a negative regulatory role in innate immune response, as it can inhibit secretion of inflammatory factors, such as IL-1 and TNF-α, thereby limiting the inflammatory response and preventing lung injuries (Hoegl et al, 2009). KGF-2 specifically facilitates the proliferation, differentiation, and migration of epithelial cells, in addition to enhancing the embryonic development via induction of various signal pathways.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of interleukin-10 and recombinant human keratinocyte growth factor-2 on ventilation-induced lung injury in rats

Wu¹,

Xiong²,

Xiong³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. A rat model of ventilation-induced lung injury (VILI) during anesthesia was generated to investigate the potential role and possible mechanism of interleukin-10 (IL-10) and recombinant human keratinocyte growth factor-2 (rhKGF-2) in protecting anesthetized rats against VILI. A total of 50 male SD rats were randomly divided into 5 groups (N = 10 each): control, VILI, IL-10, rhKGF-2, and IL-10 + rhKGF-2. The VILI (model) group was generated via ventilation, with a tidal volume of 20 mL/kg. Rats in the IL-10 and rhKGF-2 groups received 8 mg/kg IL-10 and 5 mg/kg rhKGF-2, respectively, prior to ventilation. The rats in the IL-10 + rhKGF-2 group received both 8 mg/ kg IL-10 and 5 mg/kg rhKGF-2 72 h before ventilation. The total number of nucleated cells and neutrophils in the bronchial alveolar lavage fluid was quantified, and the pathological changes in the pulmonary tissues examined by hematoxylin and eosin staining. The transcript and protein levels of surfactant protein C (SP-C) in lung tissues were detected by real-time polymerase chain reaction and western blot analyses. The

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Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury

Abstract: Prophylactic inhalation of IL-10 improved survival and reduced lung injury in experimental VILI. Results indicate that this effect may be mediated by the inhibition of stress-induced inflammation and pulmonary biotrauma.

Cited by 32 publications

References 43 publications

Inflammation and matrix remodeling during repair of ventilator-induced lung injury

Inflammation and matrix remodeling during repair of ventilator-induced lung injury

Lidocaine increases the anti‐inflammatory cytokine IL‐10 following mechanical ventilation in healthy mice

Protective effect of interleukin-10 and recombinant human keratinocyte growth factor-2 on ventilation-induced lung injury in rats

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