<i>The brain needs interleukin-6 (IL-6) to maintain a “healthy” energy balance</i>. Focus on “IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons”

Lutz, Thomas

doi:10.1152/ajpregu.00426.2016

Cited by 6 publications

(7 citation statements)

References 26 publications

(29 reference statements)

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“…The different roles of pro-inflammatory cytokines in experimental drinking models have been established, suggesting that activation of neuro-immune pathways can lead to modulation of AUD-related signaling and subsequent behaviors [ 38 , 39 , 40 ]. For example, it is well known that TLR4-pathway activation occurs during chronic ethanol exposure that may result in NF-kB-mediated increases in TNF-α, IL1β and IL-6, which are involved in modulation of reward neurocircuitry and levels of GABAergic, dopaminergic, glutamatergic neurotransmission [ 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, it is well known that TLR4-pathway activation occurs during chronic ethanol exposure that may result in NF-kB-mediated increases in TNF-α, IL1β and IL-6, which are involved in modulation of reward neurocircuitry and levels of GABAergic, dopaminergic, glutamatergic neurotransmission [ 41 , 42 , 43 ]. Studies from IL-6 and IL-1β KO mice suggested that these cytokines may modulate ethanol consumption behaviors, where TNF-α and IL-6 have been assigned a role in chronic ethanol drinking [ 24 , 40 , 44 ]. Accordingly, the effects of ABX were observed on these cytokines in our study of 4-wk of DID exposure which most likely represents an acute-on-chronic condition.…”

Section: Discussionmentioning

confidence: 99%

“…Microglia are primary neuro-immune cells that produce pro-inflammatory cytokines. Acute transformation of microglia into a pro-inflammatory state prepares them to remove damaged neurons [ 38 , 40 , 43 , 46 ], yet persistent hyperactivation of microglia can contribute to more neuronal injury [ 47 ]. In our study, DID exposure induced an increase in the number of Iba-1-positive microglial cells in hippocampus, which was even further enhanced with ABX-DID treatment, indicating a higher level of neuroinflammation which was also consistent with Iba-1 mRNA expression and changes in the cytokine levels.…”

Section: Discussionmentioning

confidence: 99%

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Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking

Gao

Davies

Asatryan

2022

IJMS

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Growing evidence supports the pivotal role of the bidirectional interplay between the gut microbiota and the central nervous system during the progression of alcohol use disorder (AUD). In our previous study, supplementation with sodium butyrate (SB) in C57BL/6J mice prevented increased ethanol consumption in a binge-like drinking paradigm (DID) as a result of treatment with a non-absorbable antibiotic cocktail (ABX). In this study, we tested the hypothesis that SB protection against enhanced ABX-induced ethanol consumption in mice is partially due to modulation of neuroinflammatory responses. Pro- and anti-inflammatory cytokines, as well as changes in microglia and astrocytes were analyzed in hippocampus tissues from ABX-, SB-, ABX+SB-treated mice subjected to 4-week DID. We found that ethanol without or with ABX treatment increased mRNA levels of key brain cytokines (MCP-1, TNF-α, IL-1β, IL-6 and IL-10) while SB supplementation prevented these changes. Additionally, SB supplementation prevented changes in microglia, i.e., increase in Iba-1 positive cell number and morphology, and in astrocytes, i.e., decrease in GFAP-positive cell number, induced by combination of ethanol and ABX treatments. Our results suggest that gut microbiota metabolites can influence drinking behavior by modulation of neuroinflammation, highlighting the potential for microbiome-targeting strategies for treatment or prevention of AUD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking

Gao

Davies

Asatryan

2022

IJMS

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“…The cytokine IL-6 plays divergent roles in health and disease, supporting healthy weight maintenance in a normal physiological state, in addition to its role as an essential component of inflammatory response (Lutz, 2016, Rincon, 2012). Circulating levels of IL-6 are increased in obesity; however, these changes do not correspond with IL-6 levels in the CNS, which, instead, are reduced (Roytblat et al., 2000, Stenlöf et al., 2003).…”

Section: Discussionmentioning

confidence: 99%

Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism

et al. 2019

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SummaryChronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6.

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“…Recent claims are that IL-6 supports healthy weight maintenance in a normal physiologic state [101], and while the causes of rheumatoid cachexia are multifactorial, the excess of proinflammatory cytokines is considered to be a central feature [102]. Anorexia and body-weight loss are common complications of inflammatory states, and IL-6, along with the proinflammatory cytokines TNFa and IL-1b, has previously been found to be implicated in anorexia of inflammation and infection [103,104].…”

Section: Ra Weight and Body Compositionmentioning

confidence: 99%

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

Favalli

2020

Rheumatol Ther

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Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disorder involving inflammation and progressive destruction of the joints, affecting up to 1% of the population. The majority of patients with RA have one or more comorbid conditions, the most common being cardiovascular disease, osteoporosis, and depression, the presence of which are associated with poorer clinical outcomes and lower healthrelated quality of life. RA pathogenesis is driven by a complex network of proinflammatory cells and cytokines, and of these, interleukin-6 (IL-6) plays a key role in the chronic inflammation associated with RA. Through cell signaling that can be initiated by both membrane-bound and soluble forms of its receptor, IL-6 acts both locally to promote joint inflammation and destruction, and in the circulation to mediate extra-articular manifestations of RA, including pain, fatigue, morning stiffness, anemia, and weight loss. This narrative review describes the role of IL-6 in the pathogenesis of RA, its comorbidities, and extra-articular systemic manifestations, and examines the effects of the IL-6 receptor inhibitors sarilumab and tocilizumab on clinical endpoints of RA, patient-reported outcomes, and common comorbidities and extra-articular manifestations.

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The brain needs interleukin-6 (IL-6) to maintain a “healthy” energy balance. Focus on “IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons”

Cited by 6 publications

References 26 publications

Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking

Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking

Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism

Understanding the Role of Interleukin-6 (IL-6) in the Joint and Beyond: A Comprehensive Review of IL-6 Inhibition for the Management of Rheumatoid Arthritis

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