MACROPHAGE PROSTAGLANDIN-E(2) AND OXIDATIVE RESPONSES TO ENDOTOXIN DURING IMMUNOSUPPRESSION ASSOCIATED WITH ANESTHESIA AND TRANSFUSION

The widespread use of blood transfusion in major surgical procedures h as led to concern about the immunosuppressive effect of transfusion on patients with underlying malignancy. Transfusion may also suppress th e host response to infection. The cellular mechanisms of transfusion-a ssociated immunosuppression may involve macrophage prostaglandin E2 (P GE2) in modulating the host response to cancer and infection. We previ ously observed that the transfusion of blood increased PGE2 production by unstimulated macrophages. To investigate this PGE2 associated immu nosuppression, we studied the effect of transfusion of rats using a ph ysiological stimulus of macrophage PGE2 production, bacterial endotoxi n. In the same macrophages, we analysed intracellular oxidative activi ty. Both allogeneic and syngeneic blood transfusion were associated wi th increased PGE2 release by macrophages. This stimulation of PGE2 inc reased with duration of storage of blood. A similar effect of serum in dicated that a humoral factor was involved. Endotoxin (50 ng/ml-500 mu g/ml) stimulated PGE2 production in all transfused subjects. The lowes t endotoxin concentration gave proportionately the greatest stimulatio n. Oxidative activity was down-regulated in macrophages of transfused rats, supporting an immunosuppressive role of PGE2 Within the macropha ge. An effect of surgery on the oxidative response was also detected.