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

• Published in: Critical care medicine Vol. 29; no. 11; p. 2137
• Main Authors: Volk, T, Schmutzler, M, Engelhardt, L, Döcke, W D, Volk, H D, Konertz, W, Kox, W J
• Format: Journal Article
• Language: English
• Published: United States 01.11.2001
• Subjects: Antioxidants - therapeutic use; Cardiopulmonary Bypass; Double-Blind Method; Female; Glucocorticoids - therapeutic use; Humans; Immunosuppression; Inflammation - drug therapy; Interleukins - blood; Interleukins - metabolism; Male; Methylprednisolone - therapeutic use; Middle Aged; Pregnatrienes - therapeutic use; Preoperative Care; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/00003246-200111000-00015

During cardiopulmonary bypass, inflammation and immunosuppression is present. We measured circulating mediators and monocyte-based functions and tested the hypothesis that these variables are influenced by methylprednisolone (MP) or tirilazad mesylate (TM) treatment. Randomized, controlled, double-blind prospective trial. A university hospital. Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease. Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) compared with placebo (PL). Circulating proinflammatory markers including interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and C-reactive protein were all decreased by MP treatment but not by TM treatment. Whereas rapid increases in circulating anti-inflammatory IL-10 were superinduced by MP but not TM, plasma levels of IL-1RA and transforming growth factor beta were not altered by either treatment. Decreased ex vivo lipopolysaccharide-stimulated secretion of tumor necrosis factor alpha was prolonged after MP 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. These data confirm that, during cardiopulmonary bypass, pro- and anti-inflammatory systems are activated at the same time, whereas monocyte-based immune functions are depressed. Treatment with MP abrogates proinflammatory mediators and induces a shift toward anti-inflammation at the cost of further functional monocyte deficits, whereas treatment with TM apparently has neither anti-inflammatory nor immunosuppressive actions in this setting.