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1.
《Vaccine》2022,40(11):1594-1605
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
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冠状病毒(coronavirus,CoVs)感染主要累及肺部,但对心血管系统损伤作用也不容忽视。CoVs感染引起的心脏损伤并非罕见,其发生与病情的严重程度密切相关。本文首先从CoVs引起心血管损伤的证据入手,进一步探讨了CoVs对心肌的直接损伤,以及肾素血管紧张素(RAS)系统激活和细胞因子风暴与炎症反应对心血管损伤的可能作用机制。相关心血管损伤的可能机制包括,(1)病毒直接作用:CoVs在心肌细胞复制,损伤心肌;(2)RAS系统激活:感染CoVs后,心脏血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)的表达下调,激活RAS系统,使得血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)收缩血管功能增强,Ang1-7保护心脏效应减弱;(3)诱发细胞因子风暴:循环细胞因子和全身炎症反应引起心脏损伤;(4)其他:包括低氧血症和儿茶酚胺心脏毒性。本文就相关内容作一综述,为后续的详尽机制和治疗策略研究提供思路。 相似文献
4.
Erik de Bakker Mirthe A. M. van der Putten Martijn W. Heymans Sander W. Spiekstra Taco Waaijman Liselotte Butzelaar Vera L. Negenborn Vivian K. Beekman Erman O. Akpinar Thomas Rustemeyer Frank B. Niessen Susan Gibbs 《Experimental dermatology》2021,30(1):169-178
Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R2: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice. 相似文献
5.
Ewelina Kazimierczyk Andrzej Eljaszewicz Paula Zembko Ewa Tarasiuk Malgorzata Rusak Agnieszka Kulczynska-Przybik Marta Lukaszewicz-Zajac Karol Kaminski Barbara Mroczko Maciej Szmitkowski Milena Dabrowska Bozena Sobkowicz Marcin Moniuszko Agnieszka Tycinska 《Pharmacological reports : PR》2019,71(1):73-81
Background
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献6.
2019年12月以来,新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)在武汉暴发并蔓延至全国,给整个社会带来巨大的挑战。部分COVID-19感染者早期发病并不十分凶险,但后期会突然加速进展,病人很快进入多脏器功能衰竭的状态,李兰娟院士等提出了"细胞因子风暴"概念。但目前并没有特效药物,认为IL-6是诱发细胞因子风暴的重要通路,本文结合相关文献的复习和分析,旨在综述IL-6受体阻断剂托珠单抗在新型冠状病毒肺炎危重患者使用的可行性。 相似文献
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瘢痕疙瘩是烧伤外科研究的重要课题,其形成机制尚未完全明确,本文就其在遗传机制、免疫作用、细胞增殖与胶原代谢、细胞因子等方面的研究进展进行综述。 相似文献
9.
目的 :探讨细胞因子在慢性丙型肝炎发病机制中的作用。方法:2 0例慢性丙型肝炎患者应用干扰素联合利巴韦林抗病毒治疗 2 4周。于治疗前后用 EL ISA法检测血清 IL- 2、IFN- γ、IL- 4、IL- 10水平 ,同时检测生化和病毒指标并观察不良反应。结果:抗病毒治疗后 IL- 2、IFN- γ、IL- 4、IL- 10水平发生了明显变化。与治疗前比较 ,IL- 2、IFN- γ水平逐渐升高 ,IL- 4、IL- 10水平逐渐降低 ,其中 IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 1)。对干扰素完全应答者 15例 ,IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 5 ) ;无应答者 5例 ,IL- 2、IFN- γ、IL- 4、IL- 10水平变化无统计学意义 (P >0 .0 5 )。抗病毒治疗过程中无严重不良反应。 结论:IL - 2、IL - 4、IL - 10、IFN-γ共同参与了丙型肝炎的发病。干扰素联合利巴韦林通过调整机体的免疫状态而发挥抗病毒效应 ,IL - 2、IL - 10可以作为预测抗病毒疗效的指标之一。 相似文献
10.
Fumio Nakajima Tomohiko Asano Masamichi Hayakawa Hiroshi Nakamura 《International journal of urology》1996,3(1):s19-s21
We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–NG –monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO2 – + NO1 was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times101 U, twice, If) induced a further increase. The NO2 , + NO3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h. 相似文献