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Apoptosis and Surgical Trauma
Dysregulated Expression of Death and Survival Factors on Peripheral Lymphocytes
Giovanna Delogu, MD;
Sonia Moretti, MD;
Adriana Antonucci, MD;
Sonia Marcellini, MD;
Raffaele Masciangelo, PhD;
Giuseppe Famularo, MD, PhD;
Luciano Signore, MD;
Claudio De Simone, MD
Arch Surg. 2000;135:1141-1147.
Background Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period, including a reduction in the numbers of circulating lymphocytes. It has been claimed that this immunosuppression is associated with an increased incidence of postoperative infections.
Hypothesis Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/and survival factors associated with apoptosis that, in turn, interferes with the occurrence of postsurgical infections.
Design Fifteen subjects undergoing elective surgery under general anesthesia entered the study. The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not. The data were collected prospectively.
Main Outcome Measures Peripheral blood samples were drawn before the operation, and 24 hours and 96 hours after the operation. Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method, as well as for Fas and Fas ligand, interleukin 1converting enzyme p20/caspase-1, Bcl-2, and p35 expression. The rate of apoptotic cells was correlated with the incidence of postoperative infections.
Setting University hospital.
Results Twenty-four hours after surgery, CD4+ and CD8+ cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas ligand and interleukin 1converting enzyme p20/caspase-1 expressions than preoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the proapoptotic factor p35 was reduced. In addition, we found a relationship between the rate of the apoptotic CD8+ subset and the occurrence of infectious complications during the postoperative course. At 96 hours after surgery, the variables studied returned to the baseline levels.
Conclusions In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors. The increased apoptosis of CD8+ lymphocytes, but not of CD4+ cells, seemed to be associated with a greater risk of postsurgical infections.
From the Institute of Anesthesia and Intensive Care (Drs Delogu, Antonucci, and Signore), and the Departments of Infectious Diseases (Drs Moretti and Marcellini) and Experimental Medicine (Dr Masciangelo), "La Sapienza" University; the Department of Emergency Medicine, San Camillo (Dr Famularo); and the Department of Experimental Medicine, L'Aquila University (Dr De Simone), Rome, Italy.
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