Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis

Moura, Helena Ferreira; Hansen, Fernanda; Galland, Fabiana; Silvelo, Daiane; Rebelatto, Fernando Pezzini; Ornell, Felipe; Massuda, Raffael; Scherer, Juliana Nichterwitz; Schuch, Felipe Barreto; Kessler, Félix Henrique Paim; Diemen, Lísia von

doi:10.47626/1516-4446-2021-1893

Cited by 5 publications

(4 citation statements)

References 54 publications

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“…Thereby, we aimed to approach this matter in an in vivo microdialysis experiment and, very interestingly, our results evidence that MORs activation induces the release of the proinflammatory cytokines IL1α, IL1β, and IL6. Additionally, these cytokines participate in many pain comorbidities that involve alterations within the MCLS, among which opioid and alcohol use disorders stand out for acting through MOR (Karimi‐Haghighi et al, 2022; Moura et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Focal mu‐opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain

Cuitavi

Andrés-Herrera

Meseguer

et al. 2023

Glia

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Microglia participates in the modulation of pain signaling. The activation of microglia is suggested to play an important role in affective disorders that are related to a dysfunction of the mesocorticolimbic system (MCLS) and are commonly associated with chronic pain. Moreover, there is evidence that mu-opioid receptors (MORs), expressed in the MCLS, are involved in neuroinflammatory events, although the way by which they do it remains to be elucidated. In this study, we propose that MOR pharmacological activation within the MCLS activates and triggers the local release of proinflammatory cytokines and this pattern of activation is impacted by the presence of systemic inflammatory pain. To test this hypothesis, we used in vivo microdialysis coupled with flow cytometry to measure cytokines release in the nucleus accumbens and immunofluorescence of IBA1 in areas of the MCLS on a rat model of inflammatory pain. Interestingly, the treatment with DAMGO, a MOR agonist locally in the nucleus accumbens, triggered the release of the IL1α, IL1β, and IL6 proinflammatory cytokines. Furthermore, MOR pharmacological activation in the ventral tegmental area (VTA) modified the levels of IBA1-positive cells in the VTA, prefrontal cortex, the nucleus accumbens and the amygdala in a dose-dependent way, without impacting mechanical nociception. Additionally, MOR blockade in the VTA prevents DAMGO-induced effects. Finally, we observed that systemic inflammatory pain altered the IBA1 immunostaining derived from MOR activation in the MSCLS. Altogether, our results indicate that the microglia-MOR relationship could be pivotal to unravel some inflammatory pain-induced comorbidities related to MCLS dysfunction.

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Section: Discussionmentioning

confidence: 99%

Focal mu‐opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain

Cuitavi

Andrés-Herrera

Meseguer

et al. 2023

Glia

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“…Previous studies, especially in the depression literature, have demonstrated effects of LPS stimulation on IL‐6 (Cho et al, 2019; Irwin et al, 2006). In the alcohol field, IL‐6 has been emphasized as an important marker associated with chronic alcohol exposure (Moura et al, 2022) and withdrawal (Gruol et al, 2018; Roberts et al, 2019). Therefore, it was counter to our original hypothesis that there was neither a main effect of AUD nor an AUD × LPS stimulation effect on IL‐6 observed in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies, especially in the depression literature, have demonstrated effects of LPS stimulation on IL-6 (Cho et al, 2019;Irwin et al, 2006). In the alcohol field, IL-6 has been emphasized as an important marker associated with chronic alcohol exposure (Moura et al, 2022) and withdrawal (Gruol et al, 2018;Roberts et al, 2019).…”

Section: Re Sultsmentioning

confidence: 99%

Alcohol use disorder (AUD) is associated with enhanced sensitivity to cellular lipopolysaccharide challenge

Burnette,

Grodin,

Olmstead

et al. 2023

Alcohol: Clinical and Experimental Research

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BackgroundInflammation has been associated with alcohol use disorder (AUD). A novel method to characterize AUD‐related immune signaling involves probing Toll‐like receptor (TLR)‐4 stimulated monocyte production of intracellular cytokines (ICCs) via lipopolysaccharide (LPS). We evaluated relationships between AUD and ICC production at rest and after LPS stimulation.MethodsWe analyzed blood samples from 36 participants (AUD N = 14; Controls N = 22), collected across time, with ICC expression assessed at rest (i.e., unstimulated) and following stimulation with LPS (i.e., a total of 5 repeated unstimulated or stimulated measures/participant). Markers assessed included tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), TNF‐α and IL‐6 co‐expression, and interferon (IFN). For each marker, we constructed linear mixed models with AUD, LPS, and timepoint as fixed effects (BMI as covariate), allowing for random slope and intercept. AUD × LPS was included as an interaction.ResultsFor TLR4‐stimulated monocyte production of TNF‐α, there were effects of AUD (p < 0.01), LPS (p < 0.001), and AUD × LPS interaction (p < 0.05), indicating that individuals with AUD showed greater unstimulated‐ and stimulated monocyte expression of TNF‐α. Similarly, for TLR4‐stimulated monocyte co‐expression of TNF‐α and IL‐6, there were effects of AUD (p < 0.01), LPS (p < 0.001), and AUD × LPS interaction (p < 0.05). No AUD or LPS effects were found for IL‐6. Timepoint effects were observed on IL‐6 and TNF‐α/IL‐6 co‐expression (p < 0.001). Finally, for IFN there were also effects of AUD (p < 0.05), LPS (p < 0.001), and AUD × LPS (p < 0.001).ConclusionsIndividuals with AUD showed greater resting or unstimulated levels of intracellular monocyte expression of TNF‐α and IL‐6/TNF‐α co‐expression than controls. AUD was associated with increases in TLR4‐stimulated monocyte production of TNF‐α and co‐production of IL‐6 and TNF‐α. This is, to our knowledge, the first study to investigate relationships between AUD and monocyte production of proinflammatory cytokines, at rest and in response to TLR4 stimulation with LPS. The study extends previous findings on the roles of proinflammatory cytokines in AUD and serves as a critical proof of concept for the use of this method to probe neuroimmune mechanisms underlying AUD.

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“…The higher osteoclastic activity observed during alcohol and nicotine consumption is closely associated with increased release of serum proinflammatory mediators (Diez‐Ruiz et al., 2010; Kallala et al., 2013; Akram et al., 2017). Alcohol consumption stimulates the production of IL‐1β and TNF‐α (Moura et al., 2022), while nicotine consumption is known to elevate the production of IL‐6, IL‐1β, IL‐8 and TNF‐α (Li et al., 2017; Ryder et al., 2002; Wendell & Stein, 2001). Therefore, both alcoholism and tobacco smoking impact the production of proinflammatory mediators, which are commonly associated with the development and progression of apical periodontitis (Azuma et al., 2014; Dessaune Neto et al., 2018; Nikolic et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis

Pinto,

Fidalgo,

de Lima

et al. 2023

Int Endodontic J

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AimTo assess the periapical alveolar bone pattern and the serum levels of proinflammatory cytokines, biochemical markers and metabolites in rats subjected to chronic alcohol and nicotine consumption and induced apical periodontitis.MethodologyTwenty‐eight male Wistar rats were divided into four groups: Control, Alcohol, Nicotine and Alcohol+Nicotine. The alcohol groups were exposed to self‐administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19 μL of nicotine/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28 days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro‐computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL‐1β, IL‐4, IL‐6 and TNF‐α), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal‐Wallis test followed by Dunn's test, while one‐way anova followed by Tukey's test was performed for parametric data.ResultsThe groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL‐1β, IL‐6 and TNF‐α compared to the Control group (p < .05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH2CH2CO), n(CH2) and n(CH3). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption.ConclusionAlcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.

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Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis

Cited by 5 publications

References 54 publications

Focal mu‐opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain

Focal mu‐opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain

Alcohol use disorder (AUD) is associated with enhanced sensitivity to cellular lipopolysaccharide challenge

Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis

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