General anesthesia accompanied by surgical stress is considered to suppress immunity, presumably by directly affecting the immune system or activating the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Along with stress such as surgery, blood transfusion, hypothermia, hyperglycemia, and postoperative pain, anesthetics per se are associated with suppressed immunity during perioperative periods because every anesthetic has direct suppressive effects on cellular and neurohumoral immunity through influencing the functions of immunocompetent cells and inflammatory mediator gene expression and secretion. Particularly in cancer patients, immunosuppression attributable to anesthetics, such as the dysfunction of natural killer cells and lymphocytes, may accelerate the growth and metastases of residual malignant cells, thereby worsening prognoses. Alternatively, the anti-inflammatory effects of anesthetics may be beneficial in distinct situations involving ischemia and reperfusion injury or the systemic inflammatory response syndrome (SIRS). Clinical anesthesiologists should select anesthetics and choose anesthetic methods with careful consideration of the clinical situation and the immune status of critically ill patients, in regard to long-term mortality, morbidity, and the optimal prognosis.

RationaleThe influence of COPD exacerbation on the endothelium is not completely understood. Circulating endothelial microparticles (EMPs) are membrane vesicles in circulating blood that are shed by activated or apoptotic endothelial cells. Objective To compare EMP numbers in stable COPD patients with those during and after exacerbation. Methods We examined the EMP numbers in 80 stable COPD patients, 27 patients with exacerbated COPD, and 20 healthy non-COPD volunteers. EMPs were defined as CD144+ MPs (VE-cadherin EMPs), CD31+/CD41À MPs (PECAM EMPs), CD146 MPs (MCAM EMPs) and CD62E + EMPs (E-selectin EMPs) as analysed by FACS. Von Willebrand factor (vWF) expression was utilised to identify the origins of the EMPs. Results VE-cadherin, PECAM and E-selectin EMP numbers were significantly higher in the stable COPD patients than in the non-COPD volunteers, and they were significantly higher in the patients with exacerbated COPD than in the stable COPD patients. The majority of these increased EMPs were vWF-negative, indicating a pulmonary capillary origin. Baseline E-selectin EMP levels were significantly higher in COPD patients who experienced frequent exacerbations than in those who did not have frequent exacerbations (p<0.001). Twenty-eight days after the onset of exacerbation, E-selectin EMP levels returned to those observed in stable COPD patients, whereas PECAM EMP levels remained high. MCAM EMP numbers were not elevated in stable or exacerbated-COPD patients. Conclusions Endothelial damage, mainly in pulmonary capillaries, occurs during exacerbation and continues even after clinical symptoms disappear. Higher baseline E-selectin EMP levels may indicate COPD patients who are susceptible to exacerbation.

Interleukin (IL)-13 is a T helper 2-derived cytokine that has recently been implicated in allergic airway responses. We hypothesized that IL-13 may regulate expression of eotaxin in airway epithelium. We found that IL-13 upregulated eotaxin messenger RNA and protein synthesis in the airway epithelial cell line BEAS-2B; this effect showed synergy with tumor necrosis factor (TNF)-alpha and also was inhibited by the glucocorticoid budesonide. To establish the mechanisms of eotaxin upregulation by IL-13, cells were transfected with an eotaxin promoter-luciferase reporter plasmid and transcription was activated by IL-13 (1.7-fold) and TNF-alpha (2.8-fold). The combination of IL-13 and TNF-alpha additively activated the promoter constructs (4.1-fold). Activation of signal transducer and activator of transcription (STAT) 6 by IL-13 was confirmed by nuclear protein binding to a DNA probe derived from the eotaxin promoter. Activation of eotaxin transcription by IL-13 and the additive effect with TNF-alpha were lost in plasmids mutated at a putative STAT6 binding site. Cotransfection with a wild-type STAT6 expression vector significantly enhanced activation of the eotaxin promoter after IL-13 stimulation (6-fold induction). A significant increase of eotaxin protein secretion in the supernatant of STAT6 wild-type-transfected cells was observed after IL-13 stimulation. Cotransfection with a dominant negative STAT6 mutant expression vector inhibited activation of the eotaxin promoter by IL-13. These results indicate that IL-13 stimulates eotaxin expression in airway epithelial cells and that STAT6 plays a pivotal role in this response.

Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.

Accumulated basic and clinical data suggest that total intravenous anesthesia with propofol, cyclooxygenase antagonists, and regional anesthesia can decrease negative consequences associated with perioperative immunosuppression. Volatile anesthesia, systemic morphine administration, unnecessary blood transfusions, intraoperative hypoxia, hypotension, hypothermia, and hyperglycemia should be avoided.