Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation.
The objectives of this prospective randomized trial were to quantify immunosuppressive effects of cardiopulmonary bypass, to identify mechanisms responsible for postoperative immunosuppression, and to investigate the effects of immunomodulatory intervention on these mechanisms. Sixty patients were studied after cardiopulmonary bypass. Immunomodulatory therapy consisted of the cyclooxygenase inhibitor indomethacin, which blocks the downregulating agent prostaglandin E2, and thymopentin, which enhances T-lymphocytic activity. Twenty patients each received indomethacin either alone or combined with thymopentin. Twenty patients served as the control population. Our in vitro studies showed a decrease of CD4+ helper/inducer T cells and interleukin-2 receptor expression on T lymphocytes, while CD8+ suppressor/cytotoxic T cells and monocytes increased. Additionally, a depression of interleukin-1 and interleukin-2 synthesis as well as concurrent low gamma-interferon serum concentrations could be documented. These results indicate a downregulation of cell-mediated immune response. As an in vivo correlate of the immunomechanistic alterations, patients demonstrated an impaired delayed-type hypersensitivity response to an antigen skin test battery. These changes in immunoreactivity could be successfully counteracted by the combined immunomodulatory regimen, whereas sole indomethacin treatment could only partially restore depressed host defense parameters. With this study we could demonstrate for the first time that human lymphocytic interleukin-2 synthesis, which represents the key event among forward regulatory immune mechanisms, can be protected via in vivo immunoaugmentatory therapy and that this therapy can successfully counteract immunosuppressive effects of cardiopulmonary bypass.
Markewitz
A
A
Department of Cardiac Surgery, University of Munich, Germany.
Faist
E
E
Lang
S
S
Endres
S
S
Fuchs
D
D
Reichart
B
B
D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D016130:Immunophenotyping; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry; D016305:Thymopentin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D007375:Interleukin-1; D007376:Interleukin-2; D007371:Interferon-gamma; D016305:Thymopentin; D007213:Indomethacin