There is a mounting body of evidence to support the role of leukocytes and their products, cytokines, in the development of postoperative complications, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. On the superficial level, one can think of this inflammatory response as “bad.” From a teleologic viewpoint, however, there must be a beneficial function to any enzyme or biological system that is conserved throughout evolution. One of the primary roles of the inflammatory response, in this respect, is to promote healing, thus allowing the organism to return to normal after an injury or stress. This is often forgotten in our quest for the“ magic anticytokine bullet.” Is it possible that we have gone to the other end of the spectrum and have overlooked the beneficial role of cytokines? Another fact that is often forgotten when we talk about the role of cytokines in disease is that they are designed to function in cell-to-cell communication, not systemically. Specifically, they have a paracrine function, yet we continue to assess their levels systemically in the serum. Serum levels reflect the “overflow” of the locally produced cytokines into the systemic circulation. This, of course, can have important consequences to the patient. However, the systemic level could represent either an over- or underrepresentation of the actual interstitial levels. Perhaps the serum levels are not related to the interstitial levels, ie, where important cell-to-cell interaction occurs. Is it possible that we are measuring the wrong levels? In this issue of CHEST (see page 1604), Weissflog and colleagues set out to assess the postoperative course of pleural leukocytes and cytokine concentrations in patients with and without malignancy who had undergone thoracic surgery. However, in doing so, they have also addressed the outlined concerns. Weissflog and colleagues assessed the levels of tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, and interleukin 10. They obtained samples of chest tube drainage five times in the first 24 h after surgery and then on postoperative days 1 through 3. Corresponding serum samples were obtained, as well as one preoperative serum sample. They separated the patients based on the presence or absence of malignancy and on whether the thoracotomy was video-assisted or open. They found that in the cancer patients, all of whom had open procedures, cytokine levels were decreased compared to those in patients operated upon for nonmalignant disease. This is especially significant in light of their data showing that patients with nonmalignant disease who had open thoracotomies had increased cytokine levels compared to those who received video-assisted thoracotomies. Thus, the presence of cancer depressed local cytokine production even with the stress of an open thoracotomy, which increased local cytokine production in nonmalignant disease. More importantly, there were no differences in the serum concentrations of the three cytokines, when the two groups were compared. This lack of difference in the serum concentrations confirms previous work.1Rapellino M Pecchio F Aimo G et al.Clinical significance of tumor necrosis factor in patients with bronchogenic carcinoma and benign lung diseases: a comparative study.Int J Biol Markers. 1992; 7: 103-106PubMed Google Scholar,2Yamauchi H Kobayashi E Yoshida T et al.Changes in immune-endocrine response after surgery.Cytokine. 1998; 10: 549-554Crossref PubMed Scopus (44) Google Scholar The site of production of the cytokines measured in the chest tube drainage is not clear. However, they are locally produced, either by the cancer cells or by local inflammatory cells, and are not secreted or overflowing into the systemic circulation. Thus, by measuring cytokine levels in chest tube effluent, as a surrogate for local, interstitial cytokine levels, the authors have shown a difference between local and systemic levels. This is important information, because as stated, it is at the local level that the cytokines exert their positive and negative effects. Perhaps by knowing the local levels, we can more accurately study the cytokines as markers of disease, as prognostic indicators for morbidity and mortality, and as substances to be manipulated therapeutically to affect patient outcome. Four patients developed complications: one cardiac arrest, one stroke, one bronchopleural fistula, and one purulent pleural space infection. Staphylococcus aureus and Enterococcus species were cultured in both of the patients with the latter two complications. All of those patients who developed complications had decreased levels of the measured cytokines in the chest tube effluent, but not systemically. Again, this supports the need to measure local, not systemic, levels. All four also had cancer. Cancer is known to be a cause of immunosuppression. The etiology of this immunosuppression is multifactorial. Perhaps one of the reasons is because of the decreased production of cytokines at the local level. Some baseline level of local cytokine production may be necessary or beneficial for healing. When the local level falls below this critical level, complications could be more likely to occur. Obviously, these numbers are too small to draw any definitive cause-and-effect conclusions, but the inference is important. One caveat to these inferences and the authors’ conclusions: chest tubes can become colonized with bacteria, even if there is not a frank pleural space infection. Although colonization is uncommon in the first 3 postoperative days, it is not impossible. If present, colonization could activate the leukocytes and thus change cytokine levels in the drainage fluid. Obviously, this could affect the results. However, if activation did occur, it would tend to increase the cytokine levels, something that did not occur in these patients. Also, the authors did obtain cultures of the chest tube drainage and there was growth in only the two patients who developed complications. In summary, Weissflog and colleagues have accomplished their goal of describing the differing cytokine levels in patients with malignant and nonmalignant conditions who undergo thoracic surgery. They have also shed light on the beneficial role of cytokines in wound healing, as well as showing us that future research may need to measure local cytokine levels instead of concentrating on systemic levels.

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