Chemotactic Mediator Requirements in Lung Injury Following Skin Burns in Rats

Piccolo, M.T.S.; Wang, Yun; Sannomiya, Paulina; Piccolo, Nelson Sarto; Piccolo, M.S.; Hugli, Tony E.; Ward, Peter A.; Till, Gerd O.

doi:10.1006/exmp.1999.2263

Cited by 35 publications

(27 citation statements)

References 23 publications

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“…Skin launches a complex inflammatory response to thermal injury (7,21,38). Although this dermal inflammation is elemental to any form of wound healing, the excessive response after severe burn may induce SIRS and subsequent multiorgan failure.…”

Section: Discussionmentioning

confidence: 99%

Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model

Ipaktchi

Mattar

Niederbichler

et al. 2007

Critical Care Medicine

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Section: Discussionmentioning

confidence: 99%

Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model

Ipaktchi

Mattar

Niederbichler

et al. 2007

Critical Care Medicine

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“…Skin, a highly immunocompetent organ, reacts to burn injury via a complex inflammatory response (21,22). Although dermal inflammation is an important physiologic part of wound healing, excessive local wound inflammation may activate systemic inflammation.…”

Section: Discussionmentioning

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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“…Several investigators have used CINC and MIP-2 antiserum or antibodies to determine their roles in models of tissue injury. 8,11,20,36,[43][44][45] In the IgG immune complex-induced model of acute lung injury, specific blockade of either MIP-2 or CINC significantly reduced lung injury and reduced neutrophil accumulation. 11 Intratracheal injection of antiserum to CINC inhibits intratracheal LPS and IL-1 induced neutrophil emigration into BAL fluid by approximately 60-70%.…”

Section: Discussionmentioning

confidence: 99%

IL-1 regulates in vivo C—X—C chemokine induction and neutrophil sequestration following endotoxemia

Calkins

Bensard

Shames

et al. 2002

Journal of Endotoxin Research

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The influx of neutrophils into tissues in response to inflammatory stimuli involves C—X—C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro , but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C—X—C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blockedbyIL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1β that was decreased by IL-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1β and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.

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Chemotactic Mediator Requirements in Lung Injury Following Skin Burns in Rats

Cited by 35 publications

References 23 publications

Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model

Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model

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

IL-1 regulates in vivo C—X—C chemokine induction and neutrophil sequestration following endotoxemia

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