scholarly journals “TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia”

2017 ◽  
Author(s):  
Kevin G. Burfeind ◽  
Xinxia Zhu ◽  
Peter R. Levasseur ◽  
Katherine A. Michaelis ◽  
Mason A. Norgard ◽  
...  
Keyword(s):  
Cancer Cachexia ◽  
Sickness Behavior ◽  
Neutrophil Infiltration ◽  
Inflammatory Signaling ◽  
Lps Challenge ◽  
Hypothalamic Inflammation ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Acute Sickness ◽  
Lps Treatment

AbstractHypothalamic inflammation is a key component of acute sickness behavior and cachexia, yet mechanisms of inflammatory signaling in the central nervous system remain unclear. We assessed the role of TRIF signaling in acute inflammation (lipopolysaccharide (LPS) challenge) and in a chronic inflammatory state (cancer cachexia). TRIFKO mice resisted anorexia and weight loss after peripheral (intraperitoneal, IP) or central (intracerebroventricular, ICV) LPS challenge and in a model of pancreatic cancer cachexia. Compared to WT mice, TRIFKO mice showed attenuated upregulation of Il6, Ccl2, Ccl5, Cxcl1, Cxcl2, and Cxcl10 in the hypothalamus after IP LPS treatment, as well as attenuated microglial activation and neutrophil infiltration into the brain after ICV LPS treatment. Our results show that TRIF is an important inflammatory signaling mediator of sickness behavior and cachexia and presents a novel therapeutic target for these conditions.

scholarly journals TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia

2018 ◽  
Vol 73 ◽  
pp. 364-374 ◽  
Author(s):  
Kevin G. Burfeind ◽  
Xinxia Zhu ◽  
Peter R. Levasseur ◽  
Katherine A. Michaelis ◽  
Mason A. Norgard ◽  
...  
Keyword(s):  
Cancer Cachexia ◽  
Inflammatory Mediator ◽  
Sickness Behavior ◽  
Acute Sickness

scholarly journals Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number, independent of microglial inflammatory signaling

2020 ◽  
Author(s):  
Caroline J. Smith ◽  
Marcy A. Kingsbury ◽  
Julia E. Dziabis ◽  
Richa Hanamsagar ◽  
Karen E. Malacon ◽  
...  
Keyword(s):  
Social Behavior ◽  
Neural Circuits ◽  
Critical Role ◽  
Sickness Behavior ◽  
Cell Number ◽  
Anterior Cingulate ◽  
Inflammatory Signaling ◽  
Lps Challenge ◽  
Female Specific ◽  
The Impact

AbstractDecreases in social behavior are a hallmark aspect of acute “sickness behavior” in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, independent of microglial inflammatory signaling.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals 233 NaturSafe® supplementation mitigates some aspects of the acute phase immune response to a lipopolysaccharide (LPS) challenge in weaned beef calves

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 117-117
Author(s):  
Nicole C Burdick Sanchez ◽  
Jeffery A Carroll ◽  
Paul R Broadway ◽  
Tom S Edrington ◽  
Ilkyu Yoon ◽  
...  
Keyword(s):  
Acute Phase ◽  
Treatment Time ◽  
Sickness Behavior ◽  
Serum Cortisol ◽  
Post Challenge ◽  
Serum Samples ◽  
Lps Challenge ◽  
Time Interaction ◽  
Tnf Α ◽  
Monitoring Devices

Abstract This study was conducted to determine if feeding calves NaturSafe would reduce the acute phase response (APR) to lipopolysaccharide (LPS) challenge. Crossbred steers (n=32; 274±2 kg) were randomly allotted to two treatment diets: 1) Control, fed a standard receiving ration, and 2) NaturSafe, fed the Control ration supplemented with NaturSafe at 12 g/hd/d (NaturSafe®, Diamond V). On d22, steers were fitted with indwelling jugular catheters and rectal temperature monitoring devices and placed in individual stalls. On d23, steers were challenged i.v. with 0.25 µg/kg BW LPS. Serum samples were collected and sickness behavior scores (SBS) recorded at 0.5-h intervals from -2 to 8h and at 24h relative to LPS challenge. Rectal temperatures were greater (P=0.01) in NaturSafe compared to Control steers for the following time intervals following LPS challenge: 6 to 11h, 13h, 15 to 20h, and 22 to 24h. Additionally, SBS were reduced (P< 0.01) in NaturSafe compared to Control steers. White blood cell concentrations were greater (P=0.05) in NaturSafe compared to Control steers prior to the LPS challenge, yet the response to LPS did not differ between treatments (P >0.05). A treatment × time interaction for serum cortisol concentrations (P< 0.01) showed an increase at 0.5 and 2h post-challenge but a reduction at 3h in NaturSafe compared to Control steers. Additionally, fibrinogen was greater (P< 0.01) in NaturSafe compared to Control steers. There was a treatment × time interaction (P< 0.01) for TNF-α where concentrations were reduced from 1 to 2h post-challenge in NaturSafe compared to Control steers. Serum IL-6 tended (P=0.09) to show a reduction in serum concentrations in NaturSafe compared to Control steers. There was a tendency (P=0.07) for a treatment × time interaction for IFN-γ. Overall these data suggest a priming effect of NaturSafe on the innate immune system of steers, resulting in an attenuated APR to the LPS challenge.

Modulation by dexamethasone of phospholipase A2 activities in endotoxemic guinea pigs

1995 ◽  
Vol 79 (4) ◽  
pp. 1271-1277 ◽  
Author(s):  
C. M. De Castro ◽  
M. F. Bureau ◽  
M. A. Nahori ◽  
C. H. Dumarey ◽  
B. B. Vargaftig ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Phospholipase A2 ◽  
Alveolar Macrophages ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Neutrophil Infiltration ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Intracellular Enzyme ◽  
Lps Challenge

One hour after lipopolysaccharide (LPS) administration (intravenous) in guinea pigs, alveolar macrophages are primed for an ex vivo increased secretion of arachidonic acid metabolites from the cyclooxygenase and the lipoxygenase pathways, with challenge by a second stimulus. At the same time, maximal levels of tumor necrosis factor-alpha (TNF-alpha) are observed in the circulation and in the bronchoalveolar lavage fluid. An extracellular form of phospholipase A2, corresponding probably to the low-molecular-mass type II enzyme, known to accumulate in inflammatory exudates, appears later in the serum of guinea pigs, to reach maximal levels 6 h after the LPS. Unlike the intracellular enzyme, extracellular phospholipase A2 is not increased by LPS in alveolar macrophages or in bronchoalveolar lavage fluids. After 24 h, at the time when neither TNF-alpha nor extracellular phospholipase A2 is present and priming of macrophages is over, maximal neutrophil infiltration is observed in the alveolar space of LPS-treated guinea pigs. Dexamethasone administered repeatedly during 3 days (subcutaneous) before the LPS challenge prevented both early events such as the macrophage priming and the TNF-alpha appearance and later events such as extracellular phospholipase A2 release and neutrophil recruitment.

scholarly journals Multiple Sclerosis and Obesity: Possible Roles of Adipokines

2016 ◽  
Vol 2016 ◽  
pp. 1-24 ◽  
Author(s):  
José de Jesús Guerrero-García ◽  
Lucrecia Carrera-Quintanar ◽  
Rocío Ivette López-Roa ◽  
Ana Laura Márquez-Aguirre ◽  
Argelia Esperanza Rojas-Mayorquín ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Life ◽  
Neural Tissue ◽  
Autoimmune Disorder ◽  
Susceptibility Factor ◽  
Related Risk ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

scholarly journals Muscle alterations in the development and progression of cancer-induced muscle atrophy: a review

2020 ◽  
Vol 128 (1) ◽  
pp. 25-41 ◽  
Author(s):  
Megan E. Rosa-Caldwell ◽  
Dennis K. Fix ◽  
Tyrone A. Washington ◽  
Nicholas P. Greene
Keyword(s):  
Cancer Patients ◽  
Protein Turnover ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Cell Function ◽  
Developmental Stages ◽  
Muscle Loss ◽  
Inflammatory Signaling ◽  
Mortality And Morbidity ◽  
Cancer Types

Cancer cachexia—cancer-associated body weight and muscle loss—is a significant predictor of mortality and morbidity in cancer patients across a variety of cancer types. However, despite the negative prognosis associated with cachexia onset, there are no clinical therapies approved to treat or prevent cachexia. This lack of treatment may be partially due to the relative dearth of literature on mechanisms occurring within the muscle before the onset of muscle wasting. Therefore, the purpose of this review is to compile the current scientific literature on mechanisms contributing to the development and progression of cancer cachexia, including protein turnover, inflammatory signaling, and mitochondrial dysfunction. We define “development” as changes in cell function occurring before the onset of cachexia and “progression” as alterations to cell function that coincide with the exacerbation of muscle wasting. Overall, the current literature suggests that multiple aspects of cellular function, such as protein turnover, inflammatory signaling, and mitochondrial quality, are altered before the onset of muscle loss during cancer cachexia and clearly highlights the need to study more thoroughly the developmental stages of cachexia. The studying of these early aberrations will allow for the development of effective therapeutics to prevent the onset of cachexia and improve health outcomes in cancer patients.

scholarly journals n-3 PUFA and obesity: from peripheral tissues to the central nervous system

2018 ◽  
Vol 119 (11) ◽  
pp. 1312-1323 ◽  
Author(s):  
Aline Haas de Mello ◽  
Marcela Fornari Uberti ◽  
Bianca Xavier de Farias ◽  
Nathalia Alberti Ribas de Souza ◽  
Gislaine Tezza Rezin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cardiac Arrhythmias ◽  
The Body ◽  
Low Grade ◽  
Therapeutic Approaches ◽  
Peripheral Tissues ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Inflammatory Effect

AbstractThe current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).

scholarly journals Impact of Exercise on Immunometabolism in Multiple Sclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Benefits ◽  
Demyelinating Lesions ◽  
Inflammatory State ◽  
Autoimmune Condition ◽  
The Central Nervous System ◽  
Axonal Degradation

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.

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