Objective To observe the effect of small dose of dexamethasone on the immunological cell changing and inflammatory response after the section resection of mammary gland. Methods Forty female patients scheduled for mammary gland section resection under general anesthesia were randomly divided into control group and treatment group. The two groups were subjected to general anesthesia under laryngeal mask ventilation. The treatment group was received dexamethasone 4 mg by intravenous before surgery. Blood cell classification count, blood glucose, CRP, IL-6, IL-8 level, CD4+ and CD8+ proportion and their ratios were detected before operation (t1), 24 h after operation (t2) and 48 h after operation (t3). Results Compared with the treatment group, the leucocyte count, neutrophil count and eosinophil count level at t1decreased significantly in the control group, but CRP level was higher (P<0.05), and the lymphocyte count decreased especially significant (P<0.01). Compared with t1 and t3, the proportion of CD4+, CD8+ and CD4+/CD8+ at t2 in the control group decreased significantly (P<0.05). Conclusion Intravenous injection of dexamethasone before operation can reduce the inflammatory reaction 24 h after operation via changing the number of immune cells after operation, which shows an effect on the postoperative immune system.
选择择期行乳腺区段切除术女性患者40例,年龄为25~58岁,体质量指数为18~25 kg·(m2)-1,美国麻醉医师协会(American Society of Anesthesiologists,ASA)麻醉分级为Ⅰ或Ⅱ级,所有病例均签署麻醉知情同意书。排除标准:近期服用免疫抑制药;已被确诊为恶性肿瘤,合并高血压、糖尿病、消化性溃疡;服用阿片类药物控制的慢性疼痛;对地塞米松过敏;预计进行术后静脉自控镇痛。采用随机、双盲的原则,按随机数字系统奇偶数的方法随机分为对照组和治疗组各20例。本试验经西安交通大学第二附属医院医学伦理会批准。
DHARAPS B,EKHANDES V.An observational study of incidence,risk factors & outcome of systemic inflammatory response & organ dysfunction following major trauma[J].Indian J Med Res,2017,146(3):346-353.
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CATAJ P,WANGH,GOTTUMUKKALAV,et al.Inflam-matory response,immunosuppression,and cancer recurrence after perioperative blood transfusions[J].Br J Anaesth,2013,110(5):690-701.
Debate on appropriate triggers for transfusion of allogeneic blood products and their effects on short- and long-term survival in surgical and critically ill patients continue with no definitive evidence or decisive resolution. Although transfusion-related immune modulation (TRIM) is well established, its influence on immune competence in the recipient and its effects on cancer recurrence after a curative resection remains controversial. An association between perioperative transfusion of allogeneic blood products and risk for recurrence has been shown in colorectal cancer in randomized trials; whether the same is true for other types of cancer remains to be determined. This article focuses on the laboratory, animal, and clinical evidence to date on the mechanistic understanding of inflammatory and immune-modulatory effects of blood products and their significance for recurrence in the cancer surgical patient.
CARDOSOM M,LEITEA O,SANTOSE A,et al.Effect of dexamethasone on prevention of postoperative nausea,vomiting and pain after caesarean section:a randomised,placebo-controlled,double-blind trial[J].Eur J Anaesthesiol,2013,30(3):102-105.
Context Spinal morphine is a common form of postoperative analgesia after caesarean section, but it is associated with postoperative nausea and vomiting.Objective To evaluate the hypothesis that dexamethasone reduces nausea and vomiting in patients undergoing caesarean section under spinal anaesthesia with morphine.Design Interventional, randomised, double-blinded, placebo-controlled study to evaluate a preoperative single dose of dexamethasone.Setting Patients from a tertiary hospital in the city of Sao Paulo, Sao Paulo, Brazil observed from 1 January through 30 June 2008.Patients or other participants Seventy full-term pregnant patients (American Society of Anesthesiologists 1 or 2) were studied. Patients were randomly allocated into two groups determined by a computerised table. Exclusion criteria were contraindication to regional anaesthesia, allergy to dexamethasone, opioids or local anaesthetics, hypertension or diabetes originated during pregnancy and use of any antiemetic drug received before surgery. Spinal anaesthesia consisted of hyperbaric bupivacaine and morphine.Intervention Patients received either dexamethasone 10mg in 100 ml of isotonic saline, intravenously or 100 ml of isotonic saline (placebo) prior to surgery.Main outcome Incidence of postoperative nausea and vomiting in the first 24 h were rated and recorded. Pain scores at rest and on movement were evaluated using a visual analogue scale.Results During the first 24 hours, nausea occured in 12/35 (34.4%) patients receiving dexamethasone and in 32/35 (91.4%) receiving placebo (P Conclusion Dexamethasone reduced the cumulative incidence of nausea and vomiting after caesarean section under spinal anaesthesia with morphine and lowered pain scores on the first postoperative day. Eur J Anaesthesiol 2013; 30:102-105
MEHRAN,SHARPA,LORENTED,et al.Neutrophil to ly-mpocyte ratio in castration-resistant prostate cancer patients treated with daily oral corticosteroids[J].Clin Genitourin Cancer,2017,15(6):678-684.
BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to be highly prognostic across many tumor types, and predictive of treatment outcome in advanced prostate cancer, and has been postulated to be an indirect measure of tumor inflammation. We evaluated the effect of low-dose steroids on NLR in men suffering from castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: The NLR was evaluated in a prospective randomized phase II trial that compared prednisolone 5 mg twice daily and dexamethasone 0.5 mg daily administered to 75 chemotherapy and abiraterone/enzalutamide-naive CRPC patients. NLR was examined at baseline (BL), after 6 and 12 weeks of corticosteroid treatment; associations with >50% prostate-specific antigen (PSA) response, duration of response (PSA progression-free interval), and overall survival (OS) were tested using logistic regression and Cox regression analysis. RESULTS: The median NLR for all evaluable patients was 2.6 at BL; 2.9 at 6 weeks; and 4.0 at 12 weeks. After low-dose corticosteroid initiation, 46 patients had a decline in PSA with 24 confirmed responders. BL NLR (log10) associated with a PSA response (odds ratio, .029, 95% confidence interval [CI], .002-.493; P = .014), and with the extent of the PSA decline (P = .009). A favorable BL NLR (less than median) associated with a 5.5-fold higher odds of a PSA >50% response (95% CI, 1.3-23.9; P = .02). Higher BL NLR (log10) associated with a shorter time to PSA progression (hazard ratio [HR], 9.5; 95% CI, 2.3-39.9; P = .002). In multivariate analysis BL NLR as a discrete variable was independently associated with PSA progression (HR, 3.5; 95% CI, 1.5-8.1; P = .003). NLR at 6 weeks was also associated with duration of benefit; in the favorable NLR category time to PSA progression was 10.8 months, for those who converted to an unfavorable (greater than median) category 4.5 months, and for those remaining in a unfavorable category only 1.5 months (95% CI, 0.5-2.5; P = .003). OS was 33.1 months (95% CI, 24.2-42.0) and 21.9 months (95% CI, 19.3-24.4) for those with an favorable and unfavorable BL NLR, respectively. CONCLUSION: Treatment-naive CRPC patients with a high BL or during-treatment NLR appear not to benefit from low-dose corticosteroids. The immunological implications of an unfavorable NLR, and whether corticosteroids might drive prostate cancer progression in patients harboring a high NLR, warrant further study.
Objective Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell-specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets.Approach and Results We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.66.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2, S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (PConclusions Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
HILLERJ G,SAMPURNOS,MILLENR,et al.Impact of celecoxib on inflammation during cancer surgery: a randomized clinical trial[J].Can J Anaesth,2017,64(5):497-505.
Abstract PURPOSE: During cancer surgery, prostaglandin-mediated inflammation may promote and activate micrometastatic disease with a consequent increase in long-term cancer recurrence. Cyclooxygenase-2 inhibitors, known to have anti-proliferative properties, may offset such perioperative perturbation. We investigated the effectiveness of these agents to minimize inflammatory changes during cancer surgery. METHODS: Following ethics approval, 32 patients who were to undergo major intracavity cancer surgery were enrolled in this prospective, randomized, clinical trial. The treatment group received 4000002mg celecoxib preoperatively followed by five 2000002mg 12-hourly doses. The control group received no anti-inflammatory agents. Inflammatory and immunomodulatory end points were measured serially. The primary end points were the measured plasma and urinary prostaglandin E metabolite (PGE M ) levels 480002hours following surgery. Secondary endpoints included interleukin levels, leucocyte profile, and clinical end points. RESULTS: No differences in the 48-hr plasma or urinary PGE M levels were observed between the celecoxib and control groups. Linear mixed modeling, used to accommodate differences in baseline PGE M levels, showed that celecoxib (cf. control) administration lowered plasma PGE M over the entire 48-hr period following surgery (0205-coefficient0002=0002-0.380002pg.ml -1 ; 95% confidence interval: -0.69 to -0.06; P = 0.021). Celecoxib administration also lowered postoperative pain scores. DISCUSSION: Standard dosing of the cyclooxygenase-2 inhibitor celecoxib slightly reduced perioperative cyclooxygenase activity during cancer surgery. Given cyclooxygenase's role in cancer pathways, we recommend dose-finding studies be undertaken before prospective clinical trials are conducted testing the currently unsubstantiated hypothesis that perioperative anti-inflammatory administration improves long-term cancer outcomes. This trial was registered at: Australian New Zealand Clinical Trial Registry: ACTRN12615000041550; www.anzctr.org.au.
FRETLANDA A,SOKOLOVA,POSTRIGANOVAN,et al.Inflammatory response after laparoscopic versus open resection of colorectal liver metastases:data from the oslo-coMet trial[J].Medicine(Baltimore),2015,94(42):e1786.
Abstract In the article ''Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases Data From the Oslo-CoMet Trial'', which appeared in Volume 94, Issue 42 of Medicine, the University of Oslo was not credited as the affiliation for several authors. The article has since been corrected online.
Macrophages have been reported to initiate immunosuppression following trauma and hemorrhage, and recent experimental studies suggest a pivotal role of T-cells in maintaining immunosuppression. The aim of the present study was to investigate the interaction of APC and T-cells in humans following major surgery. First, APC and T-cells from 14 surgical patients were isolated, counted and characterized by their specific surface marker profile 2 and 2465h postoperatively. Then, these cells were co-incubated with cells of the other type, which had been isolated pre-operatively. Chemokine secretion from pre-operative cells as measured by enzyme immunoassay served as a bioassay for the function of the stimulating postoperative cells. CD3(+) T-cells and surface marker CD28 were markedly suppressed postoperatively, while CD3(+)CD25(+)CD127(-)Tregs were not suppressed. CD14(+)APC counts were increased with the most significant increase observed in CD14(+)HLA-DR(-) myeloid-derived suppressor cells. In co-cultures, APC showed increased postoperative secretion of TNF-α and IL-6 independently of whether they had been co-incubated with pre- or postoperative T-cells. T-cells incubated with CD14(+) cells 265h postoperatively secreted diminished amounts of IFN-γ. The results of the study suggest that T-cells play a pivotal role in mediating immunosuppression after major abdominal surgery.
NEALC P,MANNC D,GARCEAG,et al.Preoperative systemic inflammation and infectious complications after resection of colorectal liver metastases[J].Arch Surg,2011,146(4):471-478.
Postoperative complications are associated with a poor long-term prognosis after resection of colorectal liver metastases via an undetermined mechanism. The preoperative systemic inflammatory response, itself a predictor of poor survival, was recently shown to independently predict postoperative infectious complications after primary colorectal cancer resection.To examine the association of postoperative infectious complications with preoperative systemic inflammation and survival in patients undergoing resection of colorectal liver metastases.Retrospective study based on a prospectively updated database.A United Kingdom tertiary referral hepatobiliary unit.A total of 202 consecutive patients with colorectal liver metastases undergoing hepatectomy between January 1, 2000, and April 30, 2006.Multivariable analyses were performed to correlate preoperative and operative variables with postoperative complications and to correlate complications with long-term survival after metastasectomy.Ninety-day mortality and morbidity were 2.0% and 25.7%, respectively. The preoperative systemic inflammatory response independently predicted the development of infectious complications (P = .009) and major infectious complications (P = .005) after hepatectomy, along with performance of trisectionectomy. Infectious complications were associated with poor long-term survival after metastasectomy but lost independent significance when systemic inflammatory variables were included in multivariable analyses.The preoperative systemic inflammatory response independently predicts the development of infectious complications after colorectal liver metastases resection. Although infectious complications are associated with adverse long-term prognosis after hepatectomy, they lacked independent prognostic value when systemic inflammatory variables were also considered, suggesting that much of their prognostic value arises from their association with the preoperative systemic inflammatory response.
ZHENGY,IZUMIK,LIY,et al.Contrary regulation of bladder cancer cell proliferation and invasion by dexamethasone-mediated glucocorticoid receptor signals[J].Mol Cancer Ther,2012,11(12):2621-2632.
In patients with advanced bladder cancer, glucocorticoids are frequently given to reduce acute toxicity, particularly hyperemesis, during chemotherapy, as well as to improve cachectic conditions. However, it remains unclear whether glucocorticoids directly affect the development and progression of bladder cancer through the glucocorticoid receptor pathway. Glucocorticoid receptor expression was first investigated in human bladder cancer lines and tissue microarrays. Then, the effects of dexamethasone on glucocorticoid receptor transcription, cell proliferation, apoptosis/cell cycle, and invasion were examined in bladder cancer lines. Finally, mouse xenograft models for bladder cancer were used to assess the efficacy of dexamethasone on tumor progression. All the cell lines and tissues examined were found to express glucocorticoid receptor. Dexamethasone increased glucocorticoid receptor–mediated reporter activity and cell proliferation, and inhibited apoptosis in the presence or absence of cisplatin. In contrast, dexamethasone suppressed cell invasion, the expression of its related genes [MMP-2/MMP-9, interleukin (IL)-6, VEGF], and the activity of MMP-2/MMP-9, and also induced mesenchymal-to-epithelial transition. In addition, dexamethasone increased IκBα protein levels and cytosolic accumulation of NF-κB. In xenograft-bearing mice, dexamethasone slightly augmented the growth of the inoculated tumors but completely prevented the development of bloody ascites, suggestive of peritoneal dissemination of tumor cells, and actual metastasis. In all these assays, dexamethasone effects were abolished by a glucocorticoid receptor antagonist or glucocorticoid receptor knockdown via RNA interference. Thus, glucocorticoid receptor activation resulted in promotion of cell proliferation via inhibiting apoptosis yet repression of cell invasion and metastasis. These results may provide a basis of developing improved chemotherapy regimens, including or excluding glucocorticoid receptor agonists/antagonists, for urothelial carcinoma. Mol Cancer Ther; 11(12); 2621–32. 082012 AACR.
NAVEGANTESK C,DESOUZA G R,PEREIRAP,et al.Immune modulation of some autoimmune diseases:the critical role of macrophages and neutrophils in the innate and adaptive immunity[J].J Transl Med,2017,15(1):36.
Macrophages and neutrophils are key components involved in the regulation of numerous chronic inflammatory diseases, infectious disorders, and especially certain autoimmune disease. However, little is known regarding the contribution of these cells to the pathogenesis of autoimmune disorders. Recent studies have aimed to clarify certain important factors affecting the immunogenicity of these cells, including the type and dose of antigen, the microenvironment of the cell-antigen encounter, and the number, subset, and phenotype of these cells, which can prevent or induce autoimmune responses. This review highlights the role of macrophage subsets and neutrophils in injured tissues, supporting their cooperation during the pathogenesis of certain autoimmune diseases.
SILVAM T.When two is better than one:macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system[J].J Leukoc Biol,2010,87(1):93-106.
The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against intracellular and extracellular microbial pathogens are,respectively, macrophages and neutrophils. As a result of the common origin of the two phagocytes, they share several functionalities, including avid phagocytosis,similar kinetic behavior under inflammatory/infectious conditions, and antimicrobial and immunomodulatory activities. However, consequent to specialization during their differentiation, macrophages and neutrophils acquire distinctive, complementary features that originate different levels of antimicrobial capacities and cytotoxicity and different tissue localization and lifespan.This review highlights data suggesting the perspective that the combination of overlapping and complementary characteristics of the two professional phagocytes promotes their cooperative participation as effectors and modulators in innate immunity against infection and as orchestrators of adaptive immunity. In the concerted activities operating in antimicrobial innate immunity, macrophages and neutrophils are not able to replace each other. The common and complementary developmental,kinetic, and functional properties of neutrophils and macrophages make them the effector arms of a myeloid phagocyte system that groups neutrophils with members of the old mononuclear phagocyte system. The use by mammals of a system with two dedicated phagocytic cells working cooperatively represents an advantageous innate immune attack strategy that allows the efficient and safe use of powerful but dangerous microbicidal molecules.This crucial strategy is a target of key virulence mechanisms of successful pathogens.
NAKAGAWAM,TERASHIMAT,D'YACHKOVAY,et al.Glucocorticoid-induced granulocytosis:contribution of marrow release and demargination of intravascular granulocytes[J].Circulation,1998,98(21):2307-2313.
Effect of dexamethasone on prevention of postoperative nausea,vomiting and pain after caesarean section:a randomised,placebo-controlled,double-blind trial
When two is better than one:macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system
, 王宁, 许凤, 杨毅猛, 雷珊, 张蓬勃
