Influence of aminosteroid and glucocorticoid treatment on inflammation andimmune function during cardiopulmonary bypass

Objective: During cardiopulmonary bypass, inflammation and immunosuppressio n is present. We measured circulating mediators and monocyte-based function s and tested the hypothesis that these variables are influenced by methylpr ednisolone (MP) or tirilazad mesylate (TM) treatment. Design: Randomized, controlled, double-blind prospective trial. Setting: A university hospital. Patients. Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease. Interventions. Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) c ompared with placebo (PL). Measurements and Main Results: Circulating proinflammatory markers includin g interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and G-react ive protein were all decreased by MP treatment but not by TM treatment. Whe reas rapid increases in circulating anti-inflammatory IL-10 were superinduc ed by MP but not TM, plasma levels of IL-1RA and transforming growth factor beta were not altered by either treatment. Decreased ex vivo lipopolysacch aride-stimulated secretion of tumor necrosis factor a was prolonged after M P treatment but not after TM treatment. Perioperative stimulated secretion of IL-12 and interferon gamma was diminished in all groups, whereas ex vivo IL-1RA secretion tended to increase in all groups. Depression of monocyte surface expression of HLA-DR was significantly greater in patients treated with MP, whereas CD14 expression did not change. Conclusions., These data confirm that, during cardiopulmonary bypass, pro- and anti-inflammatory systems are activated at the same time, whereas monoc yte-based immune functions are depressed. Treatment with MP abrogates proin flammatory mediators and induces a shift toward anti-inflammation at the co st of further functional monocyte deficits, whereas treatment with TM appar ently has neither anti-inflammatory nor immunosuppressive actions in this s etting.