Alteration in the concentrations of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) in alcohol-dependent individuals without liver disease, during detoxification therapy

Νίκου, Θωμάς; Ioannidis, Anastasios; Zoga, Margarita; Tzavellas, Elias; Paparrigopoulos, Thomas; Magana, Maria; Pliatsika, Paraskevi; Nikolaou, Chryssoula; Chatzipanagiotou, Stylianos

doi:10.1016/j.drugalcdep.2016.03.022

Cited by 14 publications

(4 citation statements)

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“…Whether IL-10 immunoreactivity depression persists in abstinence is still to be determined, but other AUD models suggest that this effect is transient as protracted alcohol abstinence results in upregulation of IL-10 (Marshall et al 2013; Schunck et al 2015; Suryanarayanan et al 2016). Most importantly, this data indicates that excessive ethanol consumption elicits a neuroimmune response independent of, and prior to, peripheral immune system dysregulation observed in clinical studies of alcoholics (McClain and Cohen 1989; Nikou et al 2016; O’Halloran et al 2016). Peripheral immune reactions combined with the neuroimmune response are hypothesized as a mechanism of alcohol-induced brain damage (Crews and Vetreno 2014), but these data suggest that neuroimmune dysregulation occurs without peripheral influences (Marshall et al 2016b; Marshall et al 2013).…”

Section: Discussionmentioning

confidence: 62%

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Marshall

McKnight

Blose

et al. 2016

J Neuroimmune Pharmacol

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Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile and alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50% in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4 were altered seen in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm is restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.

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Section: Discussionmentioning

confidence: 62%

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Marshall

McKnight

Blose

et al. 2016

J Neuroimmune Pharmacol

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“…Of the 12 dysregulated cytokines/chemokines identified in our study, the proinflammatory cytokines/chemokines (TNF‐α, IL‐6, IL‐8, and IP10), the anti‐inflammatory cytokines (IL‐4 and IL‐10), and the growth factor (IL‐15) have been shown to be elevated in patients with ALD in comparison to HC or those with stable alcoholic cirrhosis . Serum IL‐7 concentration is higher in alcohol‐dependent individuals without clinical AH than HC . We found that IL‐8, a potent neutrophil chemotactic factor, was the most highly up‐regulated cytokine in AH patients and remained higher in abstinent AH patients.…”

Section: Discussionmentioning

confidence: 64%

“…(13,14,18,27,28) Serum IL-7 concentration is higher in alcohol-dependent individuals without clinical AH than HC. (29) We found that IL-8, a potent neutrophil chemotactic factor, was the most highly up-regulated cytokine in AH patients and remained higher in abstinent AH patients. In addition, IL-8 accumulation was more resistant to corticosteroid treatment than other proinflammatory cytokines, such as IL-6 and TNF-a.…”

Section: Discussionmentioning

confidence: 69%

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study

Amet

Xing

et al. 2017

Hepatology

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Alcoholic hepatitis (AH) develops only in small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls (HC) were enrolled and followed up to 12 months. At the baseline, HDC and HC had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (TNF-α, IL-6, IL-8, IP10, IL-4, IL-9, IL-10, FGF-2, IL-7, IL-15, and TGF-α), but lower levels of the anti-inflammatory macrophage-derived chemokine (MDC). AH patients also had more activated, yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of CD38 and CD69, but low levels of HLA-DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less IFN-γ in response to T cell stimulation. Upregulated IL-6, IL-8, CD38, and CD69 and downregulated MDC, HLA-DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL-6, IL-8, CD38, and CD69 were reduced, whereas levels of MDC, HLA-DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of TNF-α, IL-8, IL-10, FGF-2, and IL-7 remained higher. Conclusion: AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation. Alcohol abstinence reversed most, but not all, of the immunological abnormalities.

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“…In lung, cytokine production is disrupted by ethanol, exacerbating respiratory distress syndrome with upregulated expression of the Th3 and primarily anti-inflammatory cytokine, transforming growth factor-β (TGF-β) (19,20). In general, AUD patients, and in particular those with MDD, seem to exhibit higher levels of proinflammatory cytokines, IL-6, IL-7, TNF-α, GM-CSF, and IFN-γ, than controls (18,21). One recent study has shown that high-risk drinkers showed significantly higher mean values of the proinflammatory cytokine IL-6 than abstainers (22).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

et al. 2020

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Alcohol use disorder (AUD) is a primary, chronic and relapsing disease of brain reward, motivation and memory, which is associated with several comorbidities, including major depression and post-traumatic stress disorder. It has been revealed that Ibudilast (IBUD), a dual inhibitor of phosphodiesterase-4 and-10 and of macrophage migration inhibitory factor (MIF), exerts beneficial effects on AUD in rodent models and human patients. Therefore, IBUD has attracted increasing interest, with research focusing on the elucidation of the pathogenic role of MIF and its homologue, D-dopachrome tautomerase (DDT), in the pathogenesis and maintenance of AUD. By using DNA microarray analysis, the current study performed a transcriptomic expression analysis of MIF, DDT and their co-receptors, including CD74, C-X-C chemokine receptor (CXCR)2, CXCR4 and CXCR7 in patients with AUD. The results revealed that the transcriptomic levels of MIF, DDT and their receptors were superimposable in the prefrontal cortex of rodents and patients with AUD and human patients. Furthermore, peripheral blood cells from heavy drinkers exhibited a moderate increase in MIF and DDT levels, both at the baseline and following exposure to alcohol-associated cues, based on individual situations that included alcohol-related stimuli resulting in subsequent alcohol use (buying alcohol and being at a bar, watching others drink alcohol). Considering the overlapping effects of MIF and DDT, the inverse Fisher's χ 2 test was performed on unadjusted P-values to evaluate the combined effect of MIF and DDT. The results revealed a significant increase in these cytokines in heavy drinkers compared with controls (moderate drinkers). To the best of our knowledge, the present study demonstrated for the first time that MIF and DDT expression was upregulated in the blood of patients with AUD. These results therefore warrant further study to evaluate the role of MIF and DDT in the development and maintenance of AUD, to evaluate their use as biomarkers to predict the psychotherapeutic and pharmacological response of patients with AUD and for use as therapeutic targets.

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Alteration in the concentrations of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) in alcohol-dependent individuals without liver disease, during detoxification therapy

Cited by 14 publications

References 100 publications

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

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