CONTRIBUTION OF TUMOR NECROSIS FACTOR-A TO PULMONARY CYTOKINE EXPRESSION AND LUNG INJURY AFTER HEMORRHAGE AND RESUSCITATION

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 anti-mouse 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.