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-alp ha) in producing acute inflammatory lung injury after hemorrhage and r esuscitation. Design: Prospective, controlled animal study. Setting: R esearch laboratory. Subjects: Male BALB/c mice. Interventions: Treatme nt with rat anti-mouse monoclonal anti-TNF-alpha antibodies or control rat immunoglobulin G 1 hr after 30% blood volume hemorrhage and resus citation. Measurements and Main Results: Therapy with monoclonal anti- TNF-alpha antibodies prevented the posthemorrhage increases in pulmona ry TNF-alpha and interferon-gamma protein levels that normally occur a fter blood loss, Administration of monoclonal anti-TNF-alpha antibodie s also diminished the increases in interleukin-1 beta interleukin-6, a nd interleukin-10 mRNA, but not the increases in TNF-alpha and interfe ron-gamma mRNA, which are found in the lungs following hemorrhage. In addition, therapy with monoclonal anti-TNF-alpha antibodies was associ ated with significant improvement in the histologic parameters of post hemorrhage lung injury, particularly intra-alveolar hemorrhage and pul monary vascular congestion. Conclusions: These results indicate that T NF-alpha has an important role in the development of acute inflammator y lung injury after blood loss, Blockade of TNF-alpha with monoclonal antibodies significantly reduces hemorrhage-induced lung injury.