Results

In models of acute IgM-mediated RBC incompatibility in experimental HTRs, plasma TNF-alpha rise sharply in a dose-and time-dependent manner, peaking at 2 hours. It is responsible for fever, hypotension and capillary leak leading to acute shock. After 4-6 hours levels of interleukin-8 and MCP-1, monocyte chemoattractants and activators of neutrophils rise, and remain in plasma significantly elevated 48 hours. In IgG-mediated HTRs, within 6 hours the concentrations of IL-1, IL-6, and IL-8 increase significantly and remain elevated next 24 hours, resulting in fever, hypotension, leucocytosis, shock, the proliferation of T-cells and stimulation of immunoglobulin production. Cytokines also play an important role in the development of disseminated intravascular coagulation (DIC). It is associated with the activation of tissue factor pathway and promoting of hypercoagulable state by their effects on endothelial cells. IL-1 and tumor necrosis factor (TNF) induce changes in the hemostatic properties of endothelial cells surface which leads to increased tissue factor and decrease thrombomodulin expression and suppression of protein C activity. Thrombin, bradykinin, epinephrine and IL-1 activation induce acute renal failure, which leads to renal hypoperfusion and widespread fibrin deposition. In etiology of acute lung injury participate: TNF, releasing large quantities of enzyme neutrophil elastase via neutrophil degranulation and pulmonary capillary endothelial injury. IL-8 and MCP-1 released from endothelial cells also promote localised inflammation and thrombosis.

Conclusion

IL-1, TNF-alpha and IL-6 and IL-8 are all critical mediators of immune and inflammatory response and are known to synergize with each other in a number of in vitro systems. They are responsible for major signs of acute hemolytic transfusion reaction. A future therapeutic strategy of HTRs has to be aimed at modulation of underlying pathophysiologic alterations triggered by HTRs.