INTERLEUKIN-6 PRODUCTION IN HEMORRHAGIC-SHOCK IS ACCOMPANIED BY NEUTROPHIL RECRUITMENT AND LUNG INJURY

Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syn drome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) cont ributes to PMN infiltration and lung damage in HS, we examined the lun gs of rats subjected to unresuscitated and resuscitated HS for the pro duction of IL-6 and activation of Stat3. Using semiquantitative RT-PCR , we found a striking increase in IL-6 mRNA levels only in resuscitate d HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alve olar cells. Electrophoretic mobility shift assay of protein extracts f rom shock lungs exhibited an increase in Stat3 activation with kinetic s similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 act ivation predominantly within alveoli. Intratracheal instillation of IL -B alone into normal rats resulted in PMN infiltration into lung inter stitium and alveoli, marked elevation of bronchoalveolar lavage cellul arity, and increased wet-to-dry ratio. These findings indicate that IL -6 production and Stat3 activation occur early in HS and may contribut e to PMN-mediated lung injury, including ARDS after HS.