Objective: To examine the role of tumor necrosis factor-alpha (TNF-alpha) in producing acute inflammatory lung injury after hemorrhage and resuscitation.
Design: Prospective, controlled animal study.
Setting: Research laboratory.
Subjects: Male BALB/c mice.
Interventions: Treatment with rat antimouse monoclonal anti-TNF-alpha antibodies or control rat immunoglobulin G 1 hr after 30% blood volume hemorrhage and resuscitation.
Measurements and main results: Therapy with monoclonal anti-TNF-alpha antibodies prevented the posthemorrhage increases in pulmonary TNF-alpha and interferon-gamma protein levels that normally occur after blood loss. Administration of monoclonal anti-TNF-alpha antibodies also diminished the increases in interleukin-1 beta, interleukin-6, and interleukin-10 mRNA, but not the increases in TNF-alpha and interferon-gamma mRNA, which are found in the lungs following hemorrhage. In addition, therapy with monoclonal anti-TNF-alpha antibodies was associated with significant improvement in the histologic parameters of posthemorrhage lung injury, particularly intra-alveolar hemorrhage and pulmonary vascular congestion.
Conclusions: These results indicate that TNF-alpha has an important role in the development of acute inflammatory lung injury after blood loss. Blockade of TNF-alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung injury.