The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study DOI Creative Commons
James Thomas, Kirsty McGee, Md. Anower Hossain

et al.

Intensive Care Medicine Experimental, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 22, 2025

Abstract Purpose The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of treatment on inflammatory metabolomic markers. Methods Samples collected from 91 randomised STRESS-L were profiled for immune A panel pro- anti-inflammatory cytokines measured through commercially acquired multiplex Luminex assays statistically analysed by individual cluster-level analysis (patient). Metabolite fingerprinting was carried out flow infusion electrospray ionisation high-resolution mass spectrometry data using R-based platform MetaboAnalyst. metabolites identified DIMEdb (dimedb.ibers.aber.ac.uk) their mass/charge ratios. These also re-analysed analysis. individual-level models adjusted confounders, such as age, sex, noradrenaline dosage patient (random effect). Results Analysis undertaken at cluster- individual-level. There no significant differences cytokine concentration level between trial arms nor survivors non-survivors over duration observations day 1 4. Metabolomic showed some separation levels ceramides cardiolipins those who survived died. Following plasma metabolite concentrations remained different standard care succinic acid, l -tryptophan, -alanine, 2,2,2-trichloroethanol, lactic acid d -glucose. Conclusions In study ICU established tachycardia, used reduce heart rate above 95 range 80 94 beats per minute did not induce changes. -Glucose, -tryptophan trichloroethanol pathways that may merit further investigation. Trial Registration : EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 https://www.isrctn.com/ISRCTN12600919 ).

Language: Английский

Immune cell compartmentalization for brain surveillance and protection DOI
Tommaso Croese, Giulia Castellani, Michal Schwartz

et al.

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(9), P. 1083 - 1092

Published: Aug. 24, 2021

Language: Английский

Citations

139
Postprandial parasympathetic signals promote lung type 2 immunity DOI
Hongjie Chen, Xin Zhou, Tingting Liu

et al.

Neuron, Journal Year: 2025, Volume and Issue: 113(5), P. 670 - 683.e7

Published: Jan. 20, 2025

Language: Английский

Citations

2
Adaptive immunity, chronic inflammation and the clock DOI Creative Commons
Kathryn J. Gray, Julie E. Gibbs

Seminars in Immunopathology, Journal Year: 2022, Volume and Issue: 44(2), P. 209 - 224

Published: March 1, 2022

Abstract The adaptive arm of the immune system facilitates recognition specific foreign pathogens and, via action T and B lymphocytes, induces a fine-tuned response to target pathogen develop immunological memory. functionality exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking development subsets) responses challenge. Here, we discuss how circadian clock exerts influence over function system, considering roles cell intrinsic clockwork machinery extrinsic rhythmic signals. Inappropriate or misguided actions can lead autoimmune diseases such rheumatoid arthritis, ulcerative colitis multiple sclerosis. Growing evidence indicates that disturbance has negative impact on progression these chronic inflammatory examine current understanding clock-immune interactions setting conditions. A greater appreciation control immunity will facilitate further mechanisms driving disease states drive improvements diagnosis treatment diseases.

Language: Английский

Citations

44
The cancer-immune dialogue in the context of stress DOI
Yuting Ma, Guido Kroemer

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 24(4), P. 264 - 281

Published: Oct. 13, 2023

Language: Английский

Citations

34
Autoimmunity in Long Covid and POTS DOI Creative Commons

Fatema-Zahra El-Rhermoul,

Artur Fedorowski,

Philip Eardley

et al.

Oxford Open Immunology, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 1, 2023

Abstract Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these common, multi-system constitutional features such fatigue, malaise skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies identified both Covid-related disorders non-Covid disorders, implying a possible underlying autoimmune pathology. The lack of specificity findings precludes direct interpretations cause association, but their prevalence with its supporting evidence is compelling.

Language: Английский

Citations

26
Immunomodulation and immunopharmacology in heart failure DOI
George Markousis‐Mavrogenis, Lukas Baumhove, Ali A. Al‐Mubarak

et al.

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 21(2), P. 119 - 149

Published: Sept. 14, 2023

Language: Английский

Citations

22
The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives DOI Creative Commons
Ondřej Uher, Katerina Hadrava Vanova, David Taïeb

et al.

Endocrine Reviews, Journal Year: 2024, Volume and Issue: 45(4), P. 521 - 552

Published: Feb. 20, 2024

Abstract Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells adrenal medullary chromaffin tissues extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal options advanced metastatic cases have been limited. Hence, understanding role of immune system in PPGL tumorigenesis can provide essential knowledge development better therapeutic tumor management strategies, especially those with PPGLs. The first part this review outlines fundamental principles microenvironment, their cancer immunoediting, particularly emphasizing We focus on how unique pathophysiology PPGLs, such as high molecular, biochemical, imaging heterogeneity production several oncometabolites, creates a tumor-specific microenvironment immunologically “cold” tumors. Thereafter, we discuss recently published studies related to reclustering based signature. second discusses future perspectives management, including immunodiagnostic promising immunotherapeutic approaches converting into active or “hot” known immunotherapy response patient outcomes. Special emphasis placed potent immune-related strategies signatures that could be used reclassification, prognostication, these improve care prognosis. Furthermore, introduce currently available immunotherapies possible combinations other therapies an emerging targets hostile environments.

Language: Английский

Citations

10
Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis DOI Creative Commons
Mathias Jachs, Lukas Hartl, Benedikt Simbrunner

et al.

Clinical Gastroenterology and Hepatology, Journal Year: 2022, Volume and Issue: 21(9), P. 2318 - 2326.e7

Published: July 14, 2022

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol secondary prophylaxis variceal bleeding.Patients undergoing paired HVPG measurements for guiding with either or propranolol were included this retrospective analysis. All patients also underwent band ligation. Changes and systemic hemodynamics compared between 2 groups. Long-term follow-up rebleeding, acute kidney injury, nonbleeding decompensation, liver-related death analyzed applying competing risk regression.Eighty-seven (carvedilol/propranolol, n = 45/42) our study. The median baseline was 21 mm Hg (interquartile range, 18-24 Hg), 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon β-blocker initiation, decreased more strongly users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% -5%] propranolol; P .027), who achieved chronic response often (53.3% 28.6%; .034). Cumulative incidences rebleeding (Gray test, .027) (P .036) significantly lower taking propranolol. Notably, ascites development/worsening observed less commonly .012). Meanwhile, injury rates did not differ groups .255). Stratifying by status yielded similar results. prognostic value intake confirmed regression models.Carvedilol marked reductions bleeding, thus is associated death, further decompensation.

Language: Английский

Citations

36
Bioactive human Alzheimer brain soluble Aβ: pathophysiology and therapeutic opportunities DOI
Shaomin Li, Andrew M. Stern

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(8), P. 3182 - 3191

Published: April 28, 2022

Language: Английский

Citations

33
Impact of norepinephrine on immunity and oxidative metabolism in sepsis DOI Creative Commons
Joby Thoppil, Prayag Mehta,

Brett Bartels

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 7, 2023

Sepsis is a major health problem in the United States (US), constituting leading contributor to mortality among critically ill patients. Despite advances treatment underlying pathophysiology of sepsis remains elusive. Reactive oxygen species (ROS) have significant role antimicrobial host defense and inflammation its dysregulation leads maladaptive responses because excessive inflammation. There growing evidence for crosstalk between central nervous system immune response infection. The hypothalamic-pituitary adrenal axis sympathetic are two pathways that mediate this interaction. Epinephrine (Epi) norepinephrine (NE), respectively effectors these interactions. Upon stimulation, NE released from nerve terminals locally within lymphoid organs activate adrenoreceptors expressed on cells. Similarly, epinephrine secreted gland which systemically also exerts influence However, understanding specific impact neuroimmunity still infancy. In review, we focus system, specifically neurotransmitter has Norepinephrine been shown modulate cell increased anti-inflammatory blunting pro-inflammatory effects. Furthermore, there suggest involved regulating oxidative metabolism This review attempts summarize known effects

Language: Английский

Citations

19