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Ann Thorac Surg 2002;74:370-371
© 2002 The Society of Thoracic Surgeons

Invited commentary

^a Department of Cardiovascular Surgery, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France

e-mail: ccv-bloc.sec3{at}bch.ap-hop-paris.fr

This study by Dr Franke and his associates has assessed the kinetics of changes of a wide array of proinflammatory and antiinflammatory cytokines following coronary artery bypass grafting operations. Blood samples were serially taken down from 25 patients up to the fifth postoperative day, thereby allowing production from cultured monocytes/macrophages or purified lymphocytes to be monitored and correlated with serum levels. The two major messages conveyed in the article are; (1) postoperative inflammatory reactions proceed in a biphasic fashion with an initial nonspecific wave (first 23 postoperative hours) which is primarily mediated by tumor necrosis factor-, interleukin-6, and interleukin-10. A second wave (24 to 72 hours postoperatively) involves more specific mediators like interleukin-5 and interferon-. (2) Overall, the cytokine balance is somewhat shifted towards antiinflammatory effects.

Several studies have previously assessed the patterns of cytokine changes after cardiopulmonary bypass (CPB). The present one, however, displays some original features which provide further insight into the complex network of inflammatory and immune reactions triggered by extracorporeal circulation. At least three observations may bear some clinical relevance.

First, the data support the strong involvement of regulatory anti-inflammatory mechanisms demonstrated by the production of interleukins 10 and 5 in this study. Of note, lymphocyte synthesis of interleukin-5 had recovered at a time when production of the proinflammatory interferon- was still depressed. This general trend towards neutralization of the potentially harmful effects of inflammatory compounds most likely accounts for the usually good clinical tolerance of patients to CPB. This should lead to less "devilizing" CPB. Conversely, disruption of the balance between antiinflammatory and proinflammatory cytokines is probably responsible for the occurrence of postoperative CPB-related adverse events. Recent studies have shown that this balance seems to be genetically controlled, which leads to interesting perspectives. Namely, preoperative screening patients for genetic polymorphism for key inflammatory mediators might become a useful means of identifying patients at higher risk for postoperative inflammatory damage and justify preventive strategies.

Second, this study shows that postoperative inflammatory reactions are not as short-lived as usually thought on the basis of studies which, in most cases, have screened changes in cytokine levels only during the early postoperative hours. For example, interferon- synthesis by lymphocytes was still depressed 5 days after the operation. A delayed impairment in the regulatory mechanisms shifting the balance towards enhanced T-cell-derived responses might account for later adverse events, particularly sepsis. These observations then call for caution in the assessment of "antiinflammatory" strategies when the period of observation is restricted to the early postoperative hours.

A third interesting observation made possible by the design of the study is more accurate characterization of the cell sources of these proinflammatory and antiinflammatory mediators. Whereas neutrophils have been the subject of most investigations, less is known about mononuclear cells, particularly lymphocytes. The observation that the pattern of cytokine synthesis markedly differed between monocytes/macrophages and lymphocytes suggests a distinct contribution of these cell lineages to the overall inflammatory and immune responses to CPB. It might then be important to sort out whether some benefit could be drawn from therapeutic interventions targeting these cells.

It is clear that a major limitation of this study is the use of cell cultures from which results cannot be directly extrapolated to the in vivo situation. The complex and dynamic interactions between the multiple cellular and humoral pathways turned on by CPB make it impossible to conclusively establish to what extent changes observed in carefully controlled in vitro experimental conditions used in the present study reflect what occurs in patients after pump-supported coronary artery bypass operations. Nevertheless, the complexity of these interactions definitely justifies attempts at dissecting the various components of these cascades to establish a benchmark against which data collected from patients who have well-defined preoperative risk factors, and who experience postoperative complications or undergo off-pump operations can be compared. From this standpoint, the present results represent an additional step towards a better understanding the pathophysiology of the inflammatory and immune responses to CPB.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Philippe Menasché Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Menasché, P. Search for Related Content PubMed Articles by Menasché, P.