Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury
Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury
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DOI：
10.4049/jimmunol.177.11.8065
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Arbabi, Saman
中科院分区：
文献类型：
--
作者：
Ipaktchi, Kyros;Mattar, Aladdein;Arbabi, Saman
局部炎症和随后的全身炎症反应之间的关系描述得很少。在烧伤模型中，皮肤炎症反应可能是全身炎症反应综合征（SIRS）和随后的全身并发症的持续触发因素。我们假设局部减弱烧伤创面炎症信号可以控制皮肤炎症源，减轻SIRS，减轻急性肺损伤。小鼠被烧伤的体表面积达到30%。亚组采用特异性p38 MAPK抑制剂或载体，局部应用于创面。局部抑制p38 MAPK显著降低烧伤创面炎症信号和随后的全身促炎细胞因子和趋化因子的表达。体外巨噬细胞功能分析显示，接受局部抑制剂的动物血清炎症介质显著衰减。局部p38 MAPK抑制通过减少肺中性粒细胞隔离、肺细胞因子表达、显著减少肺微血管损伤和水肿形成，显著减少肺部炎症反应。尽管皮肤活化转录因子-2 （p38 MAPK的下游靶点）显著减少，但肺活化转录因子-2的表达没有减少，这表明局部抑制剂没有显著的全身吸收。这些实验证明了皮肤炎症和全身炎症反应之间有很强的相互作用。减轻局部炎症信号似乎可以有效减少烧伤后SIRS和随后的全身并发症。
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.