Adriana Antonucci

Interleukin-10 and apoptotic death of circulating lymphocytes in surgical/anesthesia trauma.

OBJECTIVE To examine the relationship between circulating interleukin-10 (IL-10) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma. METHODS Data were collected prospectively on 18 adult patients undergoing elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery (t(0)) and at 24 and 96 hours after operation (t(1) and t(2), respectively). After lymphocyte isolation, quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay. RESULTS A significantly increased frequency of apoptotic CD4(+) and CD8(+) cells (p < 0.05) was observed at t1 measurement (8.10% +/- 0.58% and 12.21% +/- 1.47% for CD4(+) and CD8(+), respectively) compared with preoperative values (1.53% +/- 0.38% and 1.32% +/- 0.45% for CD4(+) and CD8(+), respectively). Plasma IL-10 levels showed a significant elevation at both t(1) and t(2) times, peaking at t(1). At t(1), IL-10 levels were correlated with the frequency of CD4(+) and CD8(+) apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL-10 vs. apoptotic CD4(+); r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8(+)). CONCLUSION Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production. The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation.

Circulating neutrophils exhibit enhanced apoptosis associated with mitochondrial dysfunctions after surgery under general anaesthesia

Background: Evidence suggests that apoptosis plays a main role in the postoperative changes detected in the polymorphonuclear neutrophil (PMN) population. Furthermore, recent studies have demonstrated that mitochondrial alterations constitute critical events of the apoptotic cascade. In this study we investigated whether apoptosis among neutrophils taken from patients undergoing surgical trauma could be associated with perturbation of mitochondrial transmembrane potential (ΔΨm) and/or exaggerated production of mitochondrial reactive oxygen species (ROS).

Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens.

Background and objective: An alteration in production of both interleukin‐10 (IL‐10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL‐10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL‐10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL‐10 circulating concentrations. Methods: Thirty‐two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL‐10 and NO levels were measured by using an enzyme‐linked‐immunosorbent assay (ELISA) and a total NO assay kit, respectively. Results: In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 ± 2.70 mmol L−1 at t0 to 13.76 ± 1.51 mmol L−1 at t1 in Group I, P < 0.0001; 28.23 ± 2.50 mmol L−1 at t0 to 11.38 ± 0.95 mmol L−1 at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 ± 1.52 mmol L−1 in Group I, P < 0.0001; 12.52 ± 1.11 mmol L−1 in Group II, P < 0.0001, both vs. t0). There was an increase in IL‐10 concentrations (26.35 ± 3.42 pg mL−1 and 75.39 ± 8.33 pg mL−1 at t1 and t2, respectively, vs. 4.93 ± 0.31 pg mL−1 at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 ± 3.22 pg mL−1 and 69.91 ± 7.33 pg mL−1 at t1 and t2, respectively, vs. 5.50 ± 0.33 pg mL−1 at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL‐10 and NO. Conclusions: During the postoperative period, IL‐10 overproduction does not correlate with the decrease in systemic NO concentration.

General anesthesia mode does not influence endocrine or immunologic profile after open or laparoscopic cholecystectomy.

To verify the impact on stress response and the influence of anesthesia on endocrine/immunologic changes, we have investigated the plasma level of norepinephrine, cortisol, TNFalpha, and IL-6 in 46 patients scheduled for laparotomy and laparoscopic cholecystectomy at 2, 6, 12, and 24 h after the operation. Among subjects who underwent open approach, 9 received fentanyl anesthesia and 13 received isoflurane anesthesia. In the laparoscopy group, 14 patients were given fentanyl anesthesia and 10 were given isoflurane anesthesia. The results obtained confirmed that laparoscopic cholecystectomy is associated with a lesser immunoendocrine response, and the two anesthesia models do not interfere with plasma changes of the assessed hormones and cytokines.

Pancuronium bromide, a non-depolarizing muscle relaxant which promotes apoptosis of blood lymphocytes in vitro.

Background:  Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function.

Does anaesthesia influence the apoptosis pathway

The biological phenomenon called apoptosis is defined as physiological, molecular, programmed cell death. The process has been discovered and rediscovered by various biologists over the past two centuries and has acquired a number of names. The term ‘apoptosis’(Ao) was coined by Currie et al. in 1972 to represent a common type of cell death that is mechanistically distinct from necrosis as evidenced by several functional and morphological features [1]. First, apoptosis characteristically involves scattered, single cells and not cell groups as necrosis does. Second, damage to the cell membrane is a crucial event during the necrotic process; thus, necrotic cells release their contents into the interstitium, leading to a local inflammatory response. Conversely, plasma membrane integrity is relatively maintained in cells undergoing apoptosis, which is associated with rapid phagocytosis and degradation of apoptotic cells by adjacent cells or resident macrophages. This accounts for the absence of inflammation and injury in neighbouring host cells [2].