Contribution of tumor necrosis factor-alpha 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 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.