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The Journal of Thoracic and Cardiovascular Surgery, Vol 105, 15-24, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
A Markewitz, E Faist, S Lang, S Endres, D Fuchs and B Reichart
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.
ARTICLES
Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation
Department of Cardiac Surgery, University of Munich, Germany.
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