The effects of methylprednisolone on complement-mediated neutrophil activation during cardiopulmonary bypass.
Complement-mediated neutrophil activation (CMNA) has been implicated as an important pathophysiologic mechanism contributing to acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). Using cardiopulmonary bypass (CPB) as a clinical model for complement-mediated microvascular injury, we studied the effects of methylprednisolone (MPSS) pretreatment on manifestations of CMNA in 28 pediatric patients undergoing CPB. Six patients not receiving MPSS served as controls. Results demonstrated that MPSS did not prevent complement activation as noted by 4.5- and 7.7-fold increases in plasma C3a des Arg levels during and immediately after CPB, respectively. However, detectable in vivo and in vitro manifestations of CMNA were altered. Neutropenia during CPB was attenuated to 65% of prebypass values compared with 47% in the control group. Neutrophil selective chemotactic desensitization toward C5a/C5a des Arg during the on bypass and postbypass periods was evident in the control group (0.41 and 0.76 cm specific migration, respectively) and prevented in the MPSS group (1.55 and 2.00 cm specific migration, respectively). We conclude that CMNA during CPB is ameliorated and/or prevented by MPSS pretreatment. These findings suggest that MPSS pretreatment may ameliorate complement-mediated microvascular (lung) injury in CPB and ARDS.
D000706:Anaphylatoxins / Q000276:immunology; D002315:Cardiopulmonary Bypass; D002630:Chemotactic Factors / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002675:Child, Preschool; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000031:analogs & derivatives / Q000276:immunology; D015926:Complement C3a / Q000031:analogs & derivatives*; D003182:Complement C5 / Q000031:analogs & derivatives / Q000276:immunology; D015937:Complement C5a, des-Arginine; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009113:Muramidase / Q000097:blood; D009503:Neutropenia / Q000517:prevention & control; D009504:Neutrophils / Q000276:immunology*; D011183:Postoperative Complications / Q000517:prevention & control*; D011292:Premedication; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000517:prevention & control*
D000706:Anaphylatoxins; D002630:Chemotactic Factors; D003176:Complement C3; D003182:Complement C5; D015937:Complement C5a, des-Arginine; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D003165:Complement System Proteins; D009113:Muramidase; D005966:Glucuronidase; D008775:Methylprednisolone