153 : HMGB1 and TNF-alpha in an experimental model of acute lung injury (ALI) under protective conventional mechanical ventilation (CMV)

Recently, HMGB1, a macrophage cytokine and nonhistone chromatin-associated protein, has been associated with sustained inflammatory response and production of cytokines in lung injury. Therefore, the aim of this study was to measure HMGB1 and TNF-alpha levels in bronchoalveolar lavage from rabbits with severe acute lung injury (ALI) induced by tracheal infusion of warm saline. Methods: Thirty rabbits were instrumented and randomly assigned into two groups: (1) animals with no ALI (Control Group-CG; n=15); and (2) animals with severe ALI (Severe Group-SG; n=15). The groups were ventilated during 4h with CMV. After ventilation, bronchoalveolar lavage fluid (BAL) was collected so that HMGB1, TNF-alpha levels and percentage of white cell were determined. Left lung was collected for histological analysis and confirmation of lesion. Results: Lung injury decreased pulmonary compliance (SG before: 1.86±0.576>SG after: 0.67±0.24) and oxygenation (PaO2 – SG before: 427.92±89.90>SG after: 68.18±19.08mmHg). Higher levels of HMGB1 were found in SG group as compared to CG group [SG: median-62 (p25–p75=20–79)>CG: 15 (13–25) ng/mL; p=0.035] and TNF-alpha level was similar to HMGB1 level in SG and CG groups [SG: 1078 (381–1224)>CG: 45 (25–86) pg/mL; p⩽0.001]. HMGB1 and TNF-alpha showed inverse correlation with oxygenation and positive correlation between them. Neutrophil percentage and histological score were higher in SG than CG (p=0.001 and p=0.0032, respectively). Conclusions: HMGB1 and TNF-alpha are found in alveolar space and correlation is found between them and with oxygenation in this experimental model. Fapesp grants: 2011/15144-2.