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 endotoxin responsiveness of blood in terms of cytokine production. In this study, the effect of interferon-gamma (IFN-gamma) on tumour necrosis factor-alpha (TNF-alpha)-producing capacity of whole blood after severe trauma and cardiac surgery was investigated. Blood samples of severely injured patients were collected at the first day after trauma and of cardiac surgery patients before, 4 h and 2 days after cardiopulmonary bypass (CPB). The blood samples were incubated with INF-gamma (0-100 U/ml) for 20 h and subsequently lipopolysaccharide (LPS)-induced TNF-alpha production was determined. Compared to healthy donors, LPS-induced TNF-alpha production was significantly reduced in blood cultures of trauma patients on day 1 after trauma and 4 h after CPB. Pre-incubation with IFN-gamma in vitro increased endotoxin-induced TNF-alpha 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, reaching levels of untreated donors only after incubation with 100 U/ml IFN-gamma. These experiments show that hyporesponsiveness of whole blood induced by trauma or cardiac surgery with CPB is not irreversible, but can be counteracted by the immunostimulant IFN-gamma. IFN-gamma, therefore, could be applied clinically in trauma patients or after cardiac surgery to prevent or to resolve infection complications.
Flohé
S
S
Department of Trauma Surgery, University Hospital Essen, Section Surgical Research, Essen, Germany. sflohe@t-online.de
Börgermann
J
J
Lim
L
L
Schade
F U
FU
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000097:blood* / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma