Erythrocyte insufflation-induced protection against oxygen toxicity: role of cytokines.

We studied the pulmonary response of adult rats to erythrocyte (RBC) and RBC lysate insufflation to define the mechanism of RBC insufflation-induced protection against oxygen toxicity. Tracheal insufflation of 1 ml RBC (75%) or RBC lysate induced an intense pulmonary inflammatory response. Within 24 h of oxygen exposure, greater than 95% of insufflated RBCs was hemolyzed. The cell-free fraction of alveolar lavage fluids from RBC- or RBC lysate-insufflated rats had similar capacity in protecting endothelial cells against H2O2 cytotoxicity. However, RBC insufflation but not RBC lysate insufflation, protected rats against oxygen toxicity. There was marked erythrophagocytosis by alveolar macrophages of RBC-insufflated rats. Insufflation of RBCs, but not RBC lysate, resulted in production of tumor necrosis factor and interleukin 1, which could be recovered by bronchoalveolar lavages. When rats were insufflated with a combination of RBC lysate and cytokines at dosages within the range of cytokine levels achievable in alveolar lavage fluids by RBC insufflation, they became tolerant to oxygen. These results suggest that endogenously produced tumor necrosis factor and interleukin-1 as a result of RBC insufflation may play an important role in RBC insufflation-induced oxygen tolerance.