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


METHODS
Randomized, controlled, double-blind prospective trial.


METHODS
A university hospital.


METHODS
Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease.


METHODS
Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) compared with placebo (PL).


RESULTS
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.


CONCLUSIONS
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.
Volk
T
T
Department of Anesthesiology and Intensive Therapy, University Hospital Charité, Campus Mitte, Humboldt-University, Berlin, Germany.
Schmutzler
M
M
Engelhardt
L
L
Döcke
W D
WD
Volk
H D
HD
Konertz
W
W
Kox
W J
WJ
D000975:Antioxidants / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000188:drug therapy*; D007378:Interleukins / Q000097:blood / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D011281:Pregnatrienes / Q000627:therapeutic use*; D011300:Preoperative Care; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D005938:Glucocorticoids; D007378:Interleukins; D011281:Pregnatrienes; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone; C053355:tirilazad