EFFECTS OF THERAPY WITH INTERLEUKIN-1 RECEPTOR ANTAGONIST ON PULMONARY CYTOKINE EXPRESSION FOLLOWING HEMORRHAGE AND RESUSCITATION

Acute lung injury frequently develops following hemorrhage and is char acterized by increased proinflammatory cytokine levels and massive neu trophil accumulation in the lung. Blood loss produces rapid increases in IL-1 alpha and IL-1 beta mRNA expression among pulmonary cell popul ations. To examine the role of IL-1 in producing acute inflammatory lu ng injury after hemorrhage, we treated mice following hemorrhage and r esuscitation with recombinant interleukin-l receptor antagonist (IL-1R a, a competitive inhibitor of the actions of IL-1. Therapy with IL-1Ra prevented the posthemorrhage increases in pulmonary TNP-alpha levels normally found after blood loss. Administration of IL-1Ra also diminis hed the increases in IL-1 beta and IL-6 mRNA levels that occur in the lungs following hemorrhage. However, the amounts of TNA-alpha and IFN- gamma mRNA among intraparenchymal pulmonary mononuclear cells remained elevated after hemorrhage despite therapy with IL-1Ra. These results indicate that therapy with IL-1Ra in the posthemorrhage period is capa ble of normalizing the expression of some, but not all, of the proinfl ammatory cytokines whose production among pulmonary cellular populatio ns is increased by blood loss.