Interferon-gamma counteracts reduced endotoxin responsiveness of whole blood following trauma and cardiopulmonary bypass

Accidental as well as surgical trauma has been reported to cause reduced en dotoxin responsiveness of blood in terms of cytokine production. In this st udy, the effect of interferon-gamma (IFN-gamma) on tumour necrosis factor-a lpha (TNF-alpha)-producing capacity of whole blood after severe trauma and cardiac surgery was investigated. Blood samples of severely injured patient s were collected at the first day after trauma and of cardiac surgery patie nts before, 4 h and 2 days after cardiopulmonary bypass (CPB). The blood sa mples were incubated with INF-gamma (0-100 U/ml) for 20 h and subsequently lipopolysaccharide (LPS)-induced TNF-alpha production was determined. Compa red to healthy donors, LPS-induced TNF-cr production was significantly redu ced in blood cultures of trauma patients on day 1 after trauma and 4 h afte r CPB. Pre-incubation with IFN-gamma in vitro increased endotoxin-induced T NF-a production in volunteers' and all patients' blood specimens in a dose- dependent manner. IFN-gamma prompted an elevation of cytokine synthesis in CPB patients' blood which equalled that of volunteers, whereas it caused a lower rise in TNF-alpha production in blood of multiply injured patients, r eaching levels of untreated donors only after incubation with 100 U/ml IFN- gamma. These experiments show that hyporesponsiveness of whole blood induce d by trauma or cardiac surgery with CPB is not irreversible, but can be cou nteracted by the immunostimulant IFN-gamma. IFN-gamma, therefore, could be applied clinically in trauma patients or after cardiac surgery to prevent o r to resolve infection complications.