The role of efalizumab in protecting ventilator-induced lung injury in anesthesia rats and related mechanisms

Although important for advanced life support and critical care, mechanical ventilation frequently caused ventilator-induced lung injury (VILI), manifesting a severe impact on survival rate. As the new generation of immunosuppressant, efalizumab was studied on a VILI model in rats to elucidate the protective function against damage and possible mechanisms. SD rats were randomly enrolled into control, VILI model, IgG control, glucocorticoid and efalizumab treated groups (N=15 each). The VILI model was generated by mechanical ventilation. In the experimental group, 2.5 mg/kg efalizumab was applied before mechanical ventilation. The total number of nuclear cells and neutrophils in bronchoalveolar lavage fluid (BALF) were counted, and the expressions of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 were also determined. Real-time PCR and Western blotting were also employed to detect the expression levels of SP-A gene and protein. Both nuclear cell and neutrophil numbers were significantly increased in VILI model group (P<0.05). The intervention by efalizumab decreased inflammatory cell number, as well as impeding the levels of cytokines such as TNF-alpha and IL-8 (P<0.05 in all cases). In VILI and IgGgroups, mRNA levels of SP-A gene were significantly decreased (P<0.05) but were potentiated by the addition of efalizumab or glucocorticoid. SP-A proteins had consistent distribution patterns as those of mRNA did. Efalizumab protects lung tissues from VILI via decreasing the activation and infiltration of inflammatory cells, inhibiting inflammatory factor release and facilitating expression of surfactant proteins.