scholarly journals CNS-Spleen Axis – a Close Interplay in Mediating Inflammatory Responses in Burn Patients and a Key to Novel Burn Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Noorisah Khan ◽  
Supreet Kaur ◽  
Carly M. Knuth ◽  
Marc G. Jeschke
Keyword(s):  
Inflammatory Responses ◽  
Immune Dysfunction ◽  
Multiple Organ ◽  
Burn Patients ◽  
Severe Burn ◽  
Therapeutic Techniques ◽  
Immune Balance ◽  
The Central Nervous System ◽  
Immune Imbalance

Severe burn-induced inflammation and subsequent hypermetabolic response can lead to profound infection and sepsis, resulting in multiple organ failure and high mortality risk in patients. This represents an extremely challenging issue for clinicians as sepsis is the leading cause of mortality in burn patients. Since hyperinflammation and immune dysfunction are a result of an immune imbalance, restoring these conditions seem to have promising benefits for burn patients. A key network that modulates the immune balance is the central nervous system (CNS)-spleen axis, which coordinates multiple signaling pathways, including sympathetic and parasympathetic pathways. Modulating inflammation is a key strategy that researchers use to understand neuroimmunomodulation in other hyperinflammatory disease models and modulating the CNS-spleen axis has led to improved clinical outcomes in patients. As the immune balance is paramount for recovery in burn-induced sepsis and patients with hyperinflammatory conditions, it appears that severe burn injuries substantially alter this CNS-spleen axis. Therefore, it is essential to address and discuss the potential therapeutic techniques that target the CNS-spleen axis that aim to restore homeostasis in burn patients. To understand this in detail, we have conducted a systematic review to explore the role of the CNS-spleen axis and its impact on immunomodulation concerning the burn-induced hypermetabolic response and associated sepsis complications. Furthermore, this thorough review explores the role of the spleen, CNS-spleen axis in the ebb and flow phases following a severe burn, how this axis induces metabolic factors and immune dysfunction, and therapeutic techniques and chemical interventions that restore the immune balance via neuroimmunomodulation.

scholarly journals The Role of Mast Cells in Stroke

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 437 ◽  
Author(s):  
Edoardo Parrella ◽  
Vanessa Porrini ◽  
Marina Benarese ◽  
Marina Pizzi
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Mast Cells ◽  
Brain Edema ◽  
Hemorrhagic Stroke ◽  
Inflammatory Responses ◽  
Adult Brain ◽  
The Central Nervous System

Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin. Through the release of preformed mediators stored in their granules and newly synthesized molecules, they are able to initiate, modulate, and prolong the immune response upon activation. Their presence in the central nervous system (CNS) has been documented for more than a century. Over the years, MCs have been associated with various neuroinflammatory conditions of CNS, including stroke. They can exacerbate CNS damage in models of ischemic and hemorrhagic stroke by amplifying the inflammatory responses and promoting brain–blood barrier disruption, brain edema, extravasation, and hemorrhage. Here, we review the role of these peculiar cells in the pathophysiology of stroke, in both immature and adult brain. Further, we discuss the role of MCs as potential targets for the treatment of stroke and the compounds potentially active as MCs modulators.

scholarly journals The predictive value of serum neopterin for multiple organ dysfunction syndrome in severe burn patients

Pteridines ◽  
2018 ◽  
Vol 29 (1) ◽  
pp. 196-200 ◽  
Author(s):  
Wei Xiong ◽  
Jun Ouyang ◽  
Hai Ci ◽  
Wenping Jiang ◽  
Wei Han ◽  
...  
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Roc Curve ◽  
Predictive Value ◽  
Multiple Organ ◽  
Burn Patients ◽  
Multiple Organ Dysfunction ◽  
Severe Burn ◽  
Serum Neopterin ◽  
Neopterin Level

AbstractObjective To investigate the predictive value of serum neopterin for multiple organ dysfunction syndrome (MODS) in severe burn patients. Methods Seventy-six severe burn patients with burns covering a total body surface area (TBSA) above 70% were included in this study. Of the 76 patients, 29 cases developed MODS (MODS group) and the remaining 47 subjects did not (non-MODS group). From the MODS group, 12 patients died (Death group) and 17 patients survived (Survive group). The serum level of neopterin in the MODS and non-MODS groups were examined by radioimmunoassay on following 1, 3 , 7 , 14 , 21 and 28 post-burn days (PBDs). A receiver operating characteristic (ROC) curve was used to analyse the predictive value of serum neopterin for MODS and death. Results The serum neopterin level in the MODS group was significantly higher than that of non-MODS group between 3~28 PBDs (p<0.001). However, the serum neopterin levels between the MODS and non-MODS groups following 1 PBD were not statistically significant (p>0.05). The best diagnostic performance of serum neopterin for MODS occurred 14 PBDs with the prediction sensitivity and specificity of 75.86% (56.46%~89.70%) and 85.11% (71.69%~93.80%) respectively. However, serum neopterin levels had no clinical value in predicting the death of MODS patients. The area under the ROC curve (AUC) was 0.72 (0.58~0.85), 0.81 (0.71~0.92) and 0.83 (0.72~0.94) for serum neopterin as biomarker in the prediction of MODS after 3, 7 and 14 PBDs, respectively. The AUCs were 0.50 (0.27~0.73), 0.53 (0.30~0.76) and 0.56 (0.33~0.79) for serum neopterin as biomarker in prediction of death for MODS patients after 3, 7 and 14 PBDs, respectively. Conclusion The persistent and significant increase of serum neopterin level is closely related to the development of MODS in patients with severe burns. Serum neopterin is therefore a promising serological marker for MODS early diagnosis, but has little efficacy in the prediction of the likelihood of death in severe burn patients with MODS.

scholarly journals The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Sun ◽  
Jin Tan ◽  
Yuyang Miao ◽  
Qiang Zhang
Keyword(s):  
Immune Regulation ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Immune Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Cellular Expression ◽  
Obstructive Sleep ◽  
Multiple Organ Injury

AbstractHypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea.

Arachidonic Acid Derivatives and Neuroinflammation

2021 ◽  
Vol 20 ◽  
Author(s):  
Era Gorica ◽  
Vincenzo Calderone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Inflammatory Responses ◽  
The Central Nervous System ◽  
The Brain ◽  
Arachidonic Acid Derivatives

: Neuroinflammation is characterized by dysregulated inflammatory responses localized within the brain and spinal cord. Neuroinflammation plays a pivotal role in the onset of several neurodegenerative disorders and is considered a typical feature of these disorders. Microglia perform primary immune surveillance and macrophage-like activities within the central nervous system. Activated microglia are predominant players in the central nervous system response to damage related to stroke, trauma, and infection. Moreover, microglial activation per se leads to a proinflammatory response and oxidative stress. During the release of cytokines and chemokines, cyclooxygenases and phospholipase A2 are stimulated. Elevated levels of these compounds play a significant role in immune cell recruitment into the brain. Cyclic phospholipase A2 plays a fundamental role in the production of prostaglandins by releasing arachidonic acid. In turn, arachidonic acid is biotransformed through different routes into several mediators that are endowed with pivotal roles in the regulation of inflammatory processes. Some experimental models of neuroinflammation exhibit an increase in cyclic phospholipase A2, leukotrienes, and prostaglandins such as prostaglandin E2, prostaglandin D2, or prostacyclin. However, findings on the role of the prostacyclin receptors have revealed that their signalling suppresses Th2-mediated inflammatory responses. In addition, other in vitro evidence suggests that prostaglandin E2 may inhibit the production of some inflammatory cytokines, attenuating inflammatory events such as mast cell degranulation or inflammatory leukotriene production. Based on these conflicting experimental data, the role of arachidonic acid derivatives in neuroinflammation remains a challenging issue.

scholarly journals A potential association between immunosenescence and high COVID-19 related mortality among elderly patients with cardiovascular diseases

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuanyuan Wang ◽  
Shu-Chao Pang ◽  
Ying Yang
Keyword(s):  
Cardiovascular Diseases ◽  
Elderly Patients ◽  
Inflammatory Responses ◽  
Virus Disease ◽  
The Elderly ◽  
Multiple Organ ◽  
Elderly Subjects ◽  
Adaptive Immune ◽  
Potential Association ◽  
Immune Imbalance

AbstractElderly patients with cardiovascular diseases account for a large proportion of Corona virus Disease 2019(COVID-19)related deaths. COVID-19, as a new coronavirus, mainly targets the patient’s lung triggering a cascade of innate and adaptive immune responses in the host. The principal causes of death among COVID-19 patients, especially elderly subjects with cardiovascular diseases, are acute respiratory distress syndrome(ARDS), multiple organ dysfunction syndrome (MODS), and microvascular thrombosis. All prompted by an excessive uncontrolled systemic inflammatory response. Immunosenescence, characterized by systemic and chronic inflammation as well as innate/adaptive immune imbalance, presents both in the elderly and cardiovascular patients. COVID-19 infection further aggravates the existing inflammatory process and lymphocyte depletion leading to uncontrollable systemic inflammatory responses, which is the primary cause of death. Based on the higher mortality, this study attempts to elucidate the pathophysiological mechanisms of COVID-19 in elderly subjects with cardiovascular diseases as well as the cause of the high mortality result from COVID-19.

scholarly journals Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase pathways

2020 ◽  
Vol 18 ◽  
Author(s):  
Aisha Siddiqui ◽  
Md Sayeed Akhtar ◽  
Zahoor Shah ◽  
Iekhsan Othman ◽  
Yatinesh Kumari
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorders ◽  
Inflammatory Responses ◽  
Biologically Active ◽  
Biochemical Pathways ◽  
Physiological Processes ◽  
The Central Nervous System ◽  
Metabolism Enzyme

: It is a known fact that inflammation affects several physiological processes, including the functioning of the central nervous system. Additionally, impairment of lipid mechanisms/pathways have been associated with a number of neurodegenerative disorders and Alzheimer’s Disease (AD) is one of them. However, much attention has been given to the link between tau and beta-amyloid hypothesis in AD pathogenesis/prognosis. Increasing evidences suggest that biologically active lipid molecules could influence the pathophysiology of AD via different mechanism of inflammation. In this review, we intend to highlight the role of inflammatory responses in the context of AD with the emphasis on biochemical pathways of lipid metabolism enzyme, 5-lipoxygenase (5-LO).

scholarly journals Role of Angiopoietin/Tie2 in Critical Illness: Promising Biomarker, Disease Mediator, and Therapeutic Target?

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Lukasz ◽  
Philipp Kümpers ◽  
Sascha David
Keyword(s):  
Critical Illness ◽  
Inflammatory Responses ◽  
Endothelial Activation ◽  
Multiple Organ ◽  
Endothelial Barrier Function ◽  
Major Step ◽  
Immune Paralysis ◽  
Broad Term ◽  
Critical Ill Patients

Critical illness is a descriptive, broad term for a serious clinical condition that can result from enormously heterogeneous etiologies. A common end feature these patients regularly suffer from is the so-called multiple organ dysfunction syndrome (MODS), often a consequence of organ hypoperfusion and ischemia, coagulopathies, overwhelming inflammatory responses, immune paralysis and mitochondrial dysfunction. Mechanistically, endothelial injury and particularly microvascular leakage is a major step in the pathophysiology of MODS and contributes to its mortality. The angiopoietin (Angpt)/Tie2 system consists of the endothelial tyrosine kinase Tie2 and its 4 circulating ligands (Angpt1-4). The balance between the agonistic ligand “Angpt-1" and the antagonistic one “Angpt-2" regulates baseline endothelial barrier function and its response to injury and is therefore considered a gatekeeper of endothelial activation. This paper provides a systematic overview of the Angpt/Tie2 system with respect to (1) its role as a global biomarker of endothelial activation in critical ill patients, (2) its contribution to MODS pathophysiology as a disease mediator, and last but not least (3) putative therapeutic applications to modify the activation state of Tie2 in mice and men.

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