Apoptosis and surgical trauma - Dysregulated expression of death and survival factors on peripheral lymphocytes

Background: Surgery and anesthesia cause depression of cell-mediated immuni ty in the postoperative period, including a reduction in the numbers of cir culating lymphocytes. It has been claimed that this immunosuppression is as sociated with an increased incidence of postoperative infections. Hypothesis: Lymphocytopenia following surgical trauma depends on a dysregul ated expression of death/and survival factors associated with apoptosis tha t, in turn, interferes with the occurrence of postsurgical infections. Design: Fifteen subjects undergoing elective surgery under general anesthes ia entered the study. The data of the patients who had infections during th e postoperative outcome were compared with the data of those who did not. T he data were collected prospectively. Main Outcome Measures: Peripheral blood samples were drawn before the opera tion, and 24 hours and 96 hours after the operation. Lymphocytes were isola ted and examined for quantification and phenotypic analysis of apoptosis us ing the 7-amino-actinomycin D method, as well as for Fas and Pas ligand, in terleukin 1-converting 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 li gand acid interleukin 1-converting enzyme p20/caspase-1 expressions than pr eoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the pro apoptotic factor p35 was reduced. In addition, we found a relationship betw een the rate of the apoptotic CD8(+) subset and the occurrence of infectiou s 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 gener al anesthesia induces an intracellular perturbation on peripheral lymphocyt es, resulting in both up-regulation of death-signaling factors and down-reg ulation of survival-signaling factors. The increased apoptosis of CD8(+) ly mphocytes, but not of CD4(+) cells, seemed to be associated with a greater risk of postsurgical infections.