Activated Nuclear Factor Kappa B and Airway Inflammation After Smoke Inhalation and Burn Injury in Sheep

Abstract

In a recent study, we have shown a rapid inflammatory cell influx across the glandular epithelium and strong proinflammatory cytokine expression at 4 hours after inhalation injury. Studies have demonstrated a significant role of nuclear factor kappa B in proinflammatory cytokine gene transcription. This study examines the acute airway inflammatory response and immunohistochemical detection of p65, a marker of nuclear factor kappa B activation, in sheep after smoke inhalation and burn injury. Pulmonary tissue from uninjured sheep and sheep at 4, 8, 12, 24, and 48 hours after inhalation and burn injury was included in the study. Following immunostaining for p65 and myeloperoxidase, the cell types and the percentage of bronchial submucosal gland cells staining for p65 and the extent of myeloperoxidase stained neutrophils in the bronchial submucosa were determined. Results indicate absence of detection of P65 before 12 hours after injury. At 12 hours after injury, strong perinuclear staining for p65 was evident in bronchial gland epithelial cells, macrophages, and endothelial cells. Bronchial submucosal gland cells showed a significant increase in the percentage of cells stained for p65 compared with uninjured animals and earlier times after injury, P < .05. At 24 and 48 hours after injury, p65 expression was evident in the bronchiolar epithelium, Type II pneumocytes, macrophages, and endothelial cells. Quantitation of the neutrophil influx into the bronchial submucosa showed a significant increase compared with uninjured tissue at 24 and 48 hours after injury, P < .05. In conclusion, immunohistochemical detection of activated p65 preceded the overall inflammatory response measured in the lamina propria. However, detection of p65 did not correlate with a recent study showing rapid emigration of neutrophils at 4 hours postinjury. Together, these results suggest that p65 immunostaining may identify cells that are activated to produce proinflammatory cytokines after injury; however, the immunoexpression may not adequately reflect the temporal activation of gene transcription that may occur with proinflammatory cytokine production with inhalation injury.

The therapeutic efficacy of Ulinastatin for rats with smoking inhalation injury

“…All of these factors play an important role in lung inflammatory injury. Cox RA et al [28] demonstrated that smoke inhalation and burn-induced lung injury was involved with the activation of NF-κB. In our present work, the results exhibited that treatment with UTI inhibited smoke inhalationinduced increase in NF-κB p65 activity and decrease in IκB-β in smoke-challenged rats.…”

“…However, UTI administration dramatically inhibited the overproduction of IL-1β, IL-6 and IL-8. JNK and NF-κB have been proved to involve with the pathogenesis of smoke inhalation-induced lung injury [27,28]. Expression of NF-κB p65 in nucleus reflects the activation of NF-κB [29].…”

Lung [18F]fluorodeoxyglucose Uptake and Ventilation–Perfusion Mismatch in the Early Stage of Experimental Acute Smoke Inhalation

“…54 These mediators reach the lung through the bronchial circulation, triggering pulmonary inflammation, dysfunction, 55 and recruiting neutrophils, which play an important role in the pathogenesis of smoke inhalation injury. 56,57 Our results indicate that progression of this inflammatory process from the airway to the pulmonary parenchyma with ensuing cell metabolic activation and associated ventilation-perfusion mismatch occur earlier than it would be inferred from previous studies showing that 24 to 48 h were needed to observe reduced PaO 2 /FiO 2 , 12,13 neutrophil infiltration 14 and NF-kB activation 15 in bronchioles and pulmonary parenchyma. This finding is important because it implies that the therapeutic window for antiinflammatory therapies 10,58 might be soon after smoke inhalation and most likely before classical manifestations of ALI appear.…”

“…An experimental study demonstrated that lung lymph flow is increased at 4 h after smoke inhalation, 11 suggesting that initial signs of pulmonary inflammation may appear earlier than the increase in shunt fraction, 12 decrease in PaO 2 /FiO 2 , 12,13 neutrophil infiltration 14 and activation of inflammatory pathways 15 that occur in the lungs of animals at 24 to 48 h after smoke inhalation. Increased uptake of glucose by pulmonary inflammatory cells is also a sign of inflammation.…”

Uso de banco de dados para caracterização de pacientes queimados internados em unidade de terapia intensiva de um hospital acadêmico terciário

“…Segue-se um período de intensa reação inflamatória com redução da produção do surfactante pulmonar, colapso e atelectasias. O aumento da permeabilidade capilar amplia a lesão das vias aéreas e o edema pulmonar (9).…”