ARDS in patients with thermal injury

Dancey, David R.; Hayes, Jason; Gómez, Manuel; Schouten, Diana; Fish, Joel; Peters, Walter; Slutsky, Arthur S.; Stewart, Thomas E.

doi:10.1007/pl00003763

Cited by 123 publications

(72 citation statements)

References 29 publications

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“…In contrast, intraperitoneal application of AAAG ODN rescued the burned mice from death, suggesting that intraperitoneally applied AAAG ODN could readily reach the injured skin and blood circulation. As shown in Figure 4, intraperitoneally applied AAAG ODN significantly reduced the levels of TNF-α and IL-6 and the Ly6G Based on the accumulated evidence, ALI, as one of main complications post burn injury, was associated with burn-induced high mortality (19). Consistently, ALI was observed in severe burn-injured mice and caused the death of the mice.…”

Section: Discussionmentioning

confidence: 74%

“…Owing to a high risk of multiple organ failure seen in burn-induced ALI (19,20), we tested whether the AAAG ODN could reduce the lung injury of the model mice. Histopathologically, at 24 h post burn injury, the lungs of burn-injured mice treated with PBS and control ODN displayed thickened and congested alveolar walls and numerous infiltrated inflammatory cells.…”

Section: Effect Of Aaag Odn On Reducing Pulmonary Inflammation In Burmentioning

confidence: 99%

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An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Xiao

et al. 2017

Mol Med

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Previously, we showed that an oligodeoxynucleotide (ODN) with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, its underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the sequence of AAAG ODN is in consensus with the interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether AAAG ODN could attenuate burn injury-induced systemic inflammatory responses by inhibiting the IRF5 pathway. Using a mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the lifespan of the mice, decreased the expression of IRF5 in the injured skin, reduced the production of TNF-α and IL-6 in the blood and injured skin, and attenuated the ALI. These effects were correlated with AAAG ODN-mediated inhibition of nuclear translocation of IRF5. The data suggest that AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5 and be developed as a drug candidate for the treatment of inflammatory diseases. online address: http://www.molmed.org

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Section: Discussionmentioning

confidence: 74%

Section: Effect Of Aaag Odn On Reducing Pulmonary Inflammation In Burmentioning

confidence: 99%

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

Xiao

et al. 2017

Mol Med

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“…None has addressed the role of neuropeptides like SP in inducing distant organ injury, such as lungs, via neurogenic inflammatory events after burn injury. Mortality resulting from multiple end-organ failure has remained the primary cause of death in critically injured individuals, with the lungs frequently being the first organ to fail (35,36). Pulmonary complications in burn individuals have been reported even when the lungs have not sustained direct thermal damage (37,38).…”

Section: Discussionmentioning

confidence: 99%

The Neuropeptide Substance P Is a Critical Mediator of Burn-Induced Acute Lung Injury

Sio

Puthia

et al. 2008

The Journal of Immunology

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The classical tachykinin substance P (SP) has numerous potent neuroimmunomodulatory effects on all kinds of airway functions. Belonging to a class of neuromediators targeting not only residential cells but also inflammatory cells, studying SP provides important information on the bidirectional linkage between how neural function affects inflammatory events and, in turn, how inflammatory responses alter neural activity. Therefore, this study aimed to investigate the effect of local burn injury on inducing distant organ pulmonary SP release and its relevance to lung injury. Our results show that burn injury in male BALB/c mice subjected to 30% total body surface area full thickness burn augments significant production of SP, preprotachykinin-A gene expression, which encodes for SP, and biological activity of SP-neurokinin-1 receptor (NK1R) signaling. Furthermore, the enhanced SP-NK1R response correlates with exacerbated lung damage after burn as evidenced by increased microvascular permeability, edema, and neutrophil accumulation. The development of heightened inflammation and lung damage was observed along with increased proinflammatory IL-1β, TNF-α, and IL-6 mRNA and protein production after injury in lung. Chemokines MIP-2 and MIP-1α were markedly increased, suggesting the active role of SP-induced chemoattractants production in trafficking inflammatory cells. More importantly, administration of L703606, a specific NK1R antagonist, 1 h before burn injury significantly disrupted the SP-NK1R signaling and reversed pulmonary inflammation and injury. The present findings show for the first time the role of SP in contributing to exaggerated pulmonary inflammatory damage after burn injury via activation of NK1R signaling.

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“…In addition to local inflammation, severe dermal burns are known to induce the systemic inflammatory response syndrome (SIRS) 3 , which correlates with a high risk of end organ failure as seen in burn-induced acute lung injury (ALI) (3,4). In the absence of inhalational injury, burn wounds are the inflammatory source triggering SIRS.…”

mentioning

confidence: 99%

Attenuating Burn Wound Inflammatory Signaling Reduces Systemic Inflammation and Acute Lung Injury

Ipaktchi¹,

Mattar²,

Niederbichler³

et al. 2006

The Journal of Immunology

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The relationship between local inflammation and the subsequent systemic inflammatory response is poorly described. In a burn injury model, the dermal inflammatory response may act as an ongoing trigger for the systemic inflammatory response syndrome (SIRS) and subsequent systemic complications. We hypothesized that topical attenuation of burn wound inflammatory signaling will control the dermal inflammatory source, attenuate SIRS, and reduce acute lung injury. Mice received a 30% total body surface area burn. Subgroups were treated with specific p38 MAPK inhibitor or vehicle, which was topically applied to wounds. Topical p38 MAPK inhibition significantly reduced burn wound inflammatory signaling and subsequent systemic expression of proinflammatory cytokines and chemokines. In vitro macrophage functional assays demonstrated a significant attenuation in serum inflammatory mediators from animals receiving the topical inhibitor. Topical p38 MAPK inhibition resulted in significantly less pulmonary inflammatory response via reduction of pulmonary neutrophil sequestration, pulmonary cytokine expression, and a significant reduction in pulmonary microvascular injury and edema formation. Although dermal activating transcription factor-2, a downstream p38 MAPK target, was significantly reduced, there was no reduction in pulmonary activating transcription factor-2 expression, arguing against significant systemic absorption of the topical inhibitor. These experiments demonstrate a strong interaction between dermal inflammation and systemic inflammatory response. Attenuating local inflammatory signaling appears effective in reducing SIRS and subsequent systemic complications after burn injury.

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ARDS in patients with thermal injury

Abstract: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.

Cited by 123 publications

References 29 publications

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

An Oligodeoxynucleotide with AAAG Repeats Significantly Attenuates Burn-induced Systemic inflammatory Responses by inhibiting interferon Regulatory Factor 5 Pathway

The Neuropeptide Substance P Is a Critical Mediator of Burn-Induced Acute Lung Injury

Attenuating Burn Wound Inflammatory Signaling Reduces Systemic Inflammation and Acute Lung Injury

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