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Ann Thorac Surg 2003;76:655-656
© 2003 The Society of Thoracic Surgeons
a Department of General Surgery, Central Military Hospital, Rübenacher Str. 170, D 56072 Koblenz, Germany
b Department of Cardiovascular Surgery, Central Military Hospital, Rübenacher Str. 170, D 56072 Koblenz, Germany
e-mail: dr.axel.franke{at}t-online.de
To the Editor:
We appreciate the comments of Drs Gu and van Oeveren regarding our report [1] about the biphasic inflammatory reaction after cardiac operations. They mentioned as limitations to the study our use of cell cultures and the lack of clinical impact of the alterations in cytokine synthesis pattern. These limitations were discussed in our study.
Their preliminary findings of depressed histocompatibility leukocyte antigen-DR (HLA-DR) expression in high-risk patients undergoing cardiac surgical procedures are interesting, although they represent an issue that was not the subject of our report. We are well aware of the fact that HLA-DR expression on monocytes is a marker for the compensatory anti-inflammatory response syndrome, as this was reported in 1996 by Volk and co-workers [2]. In addition, Misoph and associates [3] found that HLA-DR expression on monocytes was depressed to about 50% during the first 24 hours after cardiac operations with cardiopulmonary bypass. The data of Drs Gu and van Oeveren are important because they show that the depression of HLA-DR expression on monocytes of high-risk patients is more pronounced with a nadir on postoperative day 2 and has a longer duration of at least 7 days.
On day 2, we observed a switch from the nonspecific proinflammatory, monocyte-dominated first phase to a specific anti-inflammatory, type 2 T helper cell–driven second phase on postoperative days 3 through 5. Depressed on day 1, proinflammatory type 1 T helper cell cytokines (mainly interferon-
) showed a trend toward normalization at the end of our observation period (day 5). A reduction in HLA-DR expression is in line with finding depressed type 1 T helper cell–mediated proinflammatory cytokine synthesis because interferon- is a strong stimulus of monocyte and macrophage activity. The observation of beginning normalization of this synthesis capacity in our patients whereas HLA-DR expression remained depressed in the patients of Drs Gu and van Oeveren can be explained by the fact that our patients had uneventful postoperative courses whereas theirs were high-risk patients.
Sfeir [4], Grundmann [5], and their coauthors observed ongoing depression of tumor necrosis factor-
synthesis capacity and ongoing augmentation of interleukin-10 synthesis capacity of monocytes both in patients with sepsis [4] and in patients after elective cardiac operations [5]. Combining their findings with our data and those of Drs Gu and van Oeveren, we speculate that the compensatory anti-inflammatory response syndrome contributes to postoperative complications and that HLA-DR expression on monocytes represents an early marker of this development. This hypothesis awaits corroboration by further studies.
Nevertheless, although the availability of an early marker of an overwhelming compensatory anti-inflammatory response syndrome may facilitate the diagnosis of a higher susceptibility to complications, we are still left without a proven concept for treating or preventing these complications.
In addition depressed HLA-DR expression is only one piece in the exciting puzzle of the immune response after cardiac operations. Two patients in the study group of Drs Gu and van Oeveren experienced a severe complication and showed the lowest levels of HLA-DR expression postoperatively. The question of, why monocytes and macrophages did not recover to baseline in these patients was left unanswered because only one marker was assessed.
Our report and the data of Drs Gu and van Oeveren highlight perfectly the need of the following: standardized, generalized, and readily available markers for all components of the immune system, and a network for coordinated and structured immunologic investigations to obtain necessary insight into the immunologic system.
Eventually knowledge of the particulars of the nonlinear system of the human body may enable us to provide our patients with improved therapy resulting in better outcomes even in high-risk patients.
References
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