Abstract
ABSTRACT The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions characterized by inflammation, disruption of the alveolocapillary barrier, interstitial and alveolar edema, decreased lung compliance, lung hypertension, ventilation/perfusion imbalance, and refractory hypoxemia (Redding, 2001)
The experimental model, lesão pulmonar aguda (LPA) induced with warm saline in rabbit, can be used for the identification of new biomarkers
The intensity of the lesion can be monitored by PaO2 and it was used to confirm the presence of lung injury and allowed the classification of animals with different degrees and intensity of acute lung injury (ALI), but compliance only showed the ALI presence without difference in intensity of lesions
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions characterized by inflammation, disruption of the alveolocapillary barrier, interstitial and alveolar edema, decreased lung compliance, lung hypertension, ventilation/perfusion imbalance, and refractory hypoxemia (Redding, 2001). HMGB1 is a DAMP prototype and a cytokine produced by macrophages associated with severe systemic inflammatory response syndrome (SIRS), sepsis, and ALI (Scaffidi et al, 2002; Cohen, 2002). It is abundant in the cell nucleus, cytoplasm and cell membrane and is expressed in large amounts in lung tissues (Cohen, 2002). The receptor for HMGB1, called RAGE (receptor for advanced glycation end products), is usually expressed on the basolateral surface of type I pneumocytes This receptor is involved in lung development and in the injury described in ALI (Uchida et al, 2006). Expression of RAGE is higher in the lung than in other organs, a fact rendering the lung more susceptible to the effects of HMGB1 and injury by inflammatory cytokines (Uchida et al, 2006; Calfee et al, 2008; Buckley and Ehrhardt, 2010)
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