HEMORRHAGE AND RESUSCITATION INDUCE ALTERATIONS IN CYTOKINE EXPRESSION AND THE DEVELOPMENT OF ACUTE LUNG INJURY

Acute pulmonary injury occurs frequently following hemorrhage and inju ry. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in v ivo mRNA levels for cytokines with proinflammatory and immunoregulator y properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant in creases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononucle ar cells obtained 1 and 3 days after hemorrhage. Among alveolar macrop hages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception o f TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrha ged animals showed no alterations 1 day after hemorrhage, but neutroph il and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These res ults suggest that hemorrhage-induced enhancement of proinflammatory cy tokine gene transcription may be an important mechanism contributing t o the frequent development of acute lung injury following blood loss a nd injury.