The Neuroimmune Communicatome in Inflammation

Olofsson, Peder S.; Metz, Christine N.; Pavlov, Valentin A.

doi:10.1002/9783527692156.ch59

Cited by 12 publications

(9 citation statements)

References 141 publications

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“…Another observation from our study with relevance to the inflammatory reflex is the lack of effect of pyridostigmine on the anti-inflammatory cytokine IL-10. Previous findings have demonstrated that while VNS, which activates the inflammatory reflex and its efferent cholinergic arm, results in suppression of proinflammatory cytokine levels, this approach does not have an effect of IL-10 levels (Borovikova et al, 2000;Huston et al, 2006;Rosas-Ballina et al, 2011;Olofsson et al, 2017). At early stages of acute lung injury and ARDS, alveolar macrophages initiate proinflammatory signaling through the release of TNF, IL-1β and other cytokines that propagates the innate immune response and inflammation and potentiates chemokine secretion to recruit neutrophils, exudative macrophages, and lymphocytes (Herold et al, 2011;Aggarwal et al, 2014).…”

Section: Discussionmentioning

confidence: 96%

The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome

et al. 2021

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Acute respiratory distress syndrome (ARDS) is a critical illness complication that is associated with high mortality. ARDS is documented in severe cases of COVID-19. No effective pharmacological treatments for ARDS are currently available. Dysfunctional immune responses and pulmonary and systemic inflammation are characteristic features of ARDS pathogenesis. Recent advances in our understanding of the regulation of inflammation point to an important role of the vagus-nerve-mediated inflammatory reflex and neural cholinergic signaling. We examined whether pharmacological cholinergic activation using a clinically approved (for myasthenia gravis) cholinergic drug, the acetylcholinesterase inhibitor pyridostigmine alters pulmonary and systemic inflammation in mice with lipopolysaccharide (LPS)-induced ARDS. Male C57Bl/6 mice received one intratracheal instillation of LPS or were sham manipulated (control). Both groups were treated with either vehicle or pyridostigmine (1.5 mg/kg twice daily, 3 mg/day) administered by oral gavage starting at 1 h post-LPS and euthanized 24 h after LPS administration. Other groups were either sham manipulated or received LPS for 3 days and were treated with vehicle or pyridostigmine and euthanized at 72 h. Pyridostigmine treatment reduced the increased total number of cells and neutrophils in the bronchoalveolar lavage fluid (BALF) in mice with ARDS at 24 and 72 h. Pyridostigmine also reduced the number of macrophages and lymphocytes at 72 h. In addition, pyridostigmine suppressed the levels of TNF, IL-1β, IL-6, and IFN-γ in BALF and plasma at 24 and 72 h. However, this cholinergic agent did not significantly altered BALF and plasma levels of the anti-inflammatory cytokine IL-10. Neither LPS nor pyridostigmine affected BALF IFN-γ and IL-10 levels at 24 h post-LPS. In conclusion, treatments with the cholinergic agent pyridostigmine ameliorate pulmonary and systemic inflammatory responses in mice with endotoxin-induced ARDS. Considering that pyridostigmine is a clinically approved drug, these findings are of substantial interest for implementing pyridostigmine in therapeutic strategies for ARDS.

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Section: Discussionmentioning

confidence: 96%

The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome

et al. 2021

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“…The prospect that there will be ample time to find efficient strategies for obesity management has to be revised; exploring new therapeutic approaches to improve the gloomy outlook has never been of such a high priority. Bioelectronic medicine, driven by new insights into neural regulatory functions and technological developments has started to provide novel treatment options for various diseases ( Olofsson & Tracey, 2017 ; Pavlov et al, 2019 ; Pavlov & Tracey, 2019b ; Pavlov & Tracey, 2019a ) and generated interest among medical professionals, patients, caregivers, and industry ( Building a bioelectronic medicine movement 2019: insights from leaders in industry, academia, and research, 2020 ; Pavlov & Tracey, 2019a ). Important areas of current exploration of bioelectronic VNS and specifically its non-invasive forms are obesity and MetS.…”

Section: Discussionmentioning

confidence: 99%

“…Sometimes however, the normal protective course of inflammation is disrupted and inflammation becomes excessive and systemic, non-resolved, and chronic. These forms of inflammation drive the pathogenesis of numerous diseases ( Chavan, Pavlov, & Tracey, 2017 ; Olofsson, Metz, & Pavlov, 2017 ). Low-grade chronic inflammation with systemic manifestations is an important underlying event in obesity and MetS pathobiology ( Lumeng & Saltiel, 2011 ; Sutherland et al, 2004 ) ( Fig.…”

Section: Inflammation In Obesity and Metsmentioning

confidence: 99%

“…2 ). The neuro-immune dialogue through the vagus nerve takes place utilizing a “common language”; afferent vagal neurons express receptors for cytokines and other inflammatory molecules, while immune cells express receptors for acetylcholine and even synthesize acetylcholine and other neurotransmitters ( Olofsson et al, 2017 ; Terrando & Pavlov, 2018 ). The expression of IL-1β and TNF receptors, and TLR4 on afferent vagal neurons is key for sensing cytokines, LPS and other inflammatory molecules and activating signaling to NTS ( Chavan et al, 2017 ; Zanos et al, 2018 ).…”

Section: The Vagus Nerve and The Inflammatory Reflex: Mechanistic Insmentioning

confidence: 99%

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The evolving obesity challenge: targeting the vagus nerve and the inflammatory reflex in the response

Pavlov

2021

Pharmacology & Therapeutics

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Obesity and the metabolic syndrome (MetS), which have reached pandemic proportions significantly increase the risk for type 2 diabetes, cardiovascular disease, and other serious conditions. Recent data with COVID-19 patients indicate that obesity also is a significant risk factor for this novel viral disease and poor outcome of associated critical illness. These findings considerably change the view of obesity as a driver of serious, but slowly-progressing chronic diseases, and emphasize the urgency to explore new therapeutic approaches. Inflammation is a recognized driver of metabolic derangements in obesity and MetS, and a core feature of COVID-19 pathobiology. Recent advances in our understanding of inflammatory regulation have highlighted the role of the nervous system and the vagus nerve-based inflammatory reflex. Current bioelectronic and pharmacological therapeutic explorations centered on the inflammatory reflex offer new approaches for conditions characterized by immune and metabolic dysregulation and for ameliorating the escalating burden of obesity, MetS, and COVID-19.

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“…Inflammation is a vital physiological response to harmful stimuli, including pathogen invasion and tissue injury through a number of processes and pathways, including the activation of specific immune cell types (e.g., neutrophils and macrophages) and the release of inflammatory mediators (e.g., cytokines and chemokines) (Chen and Nunez, 2010; Olofsson et al, 2017). Inflammation is generally a localized event, which resolves and then the body returns to homeostasis (Chen and Nunez, 2010; Serhan and Levy, 2018).…”

Section: Vagus Nerve and Brain Cholinergic Signaling In Controlling Imentioning

confidence: 99%

Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities

2019

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Obesity and obesity-associated disorders have become world-wide epidemics, substantially increasing the risk of debilitating morbidity and mortality. A characteristic feature of these disorders, which include the metabolic syndrome (MetS) and type 2 diabetes, is chronic low-grade inflammation stemming from metabolic and immune dysregulation. Inflammation in the CNS (neuroinflammation) and cognitive impairment have also been associated with obesity-driven disorders. The nervous system has a documented role in the regulation of metabolic homeostasis and immune function, and recent studies have indicated the important role of vagus nerve and brain cholinergic signaling in this context. In this review, we outline relevant aspects of this regulation with a specific focus on obesity-associated conditions. We outline accumulating preclinical evidence for the therapeutic efficacy of cholinergic stimulation in alleviating obesity-associated inflammation, neuroinflammation, and metabolic derangements. Recently demonstrated beneficial effects of galantamine, a centrally acting cholinergic drug and cognitive enhancer, in patients with MetS are also summarized. These studies provide a rationale for further therapeutic developments using pharmacological and bioelectronic cholinergic modulation for clinical benefit in obesity-associated disorders.

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The Neuroimmune Communicatome in Inflammation

Cited by 12 publications

References 141 publications

The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome

The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome

The evolving obesity challenge: targeting the vagus nerve and the inflammatory reflex in the response

Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities

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