THE LEVEL OF SYSTEMIC INFLAMMATION AND CHANGES IN ADAPTIVE IMMUNITY IN ALCOHOLIC PSYCHOSES

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Abstract


The aim of the work is to study the level of systemic inflammation and changes in adaptive immunity in the early period after acute psychosis to assess their participation in the pathogenesis of alcoholic mental and cognitive disorders. We examined 28 patients with alcoholic psychosis (AP) and a control group of 17 healthy volunteers. Indicators of systemic inflammation and immunity, including key cytokines and lymphocyte subpopulations, were investigated. After acute psychosis of patients with alcoholism, pronounced activation of humoral immunity with impaired clearance of immune complexes, increased content and activity of Th2 with signs of insufficiency and dysfunction of Th1, reduced content and activity of cytotoxicity system cells and signs of systemic inflammation (increased CRP, cortisol, cytokines). Activation of Th2 response and an excess of proinflammatory mediators in patients with AP through various ways of interaction with the Central nervous system (n. vagus, choroidal plexus of the ventricles, and others) can participate in the disorders of metabolism of neurotransmitters in the Central nervous system involved in the pathogenesis of alcoholism, and in the maintenance of neuroinflammation. A high level of systemic inflammation can be both a trigger of psychosis and a manifestation of violations of neuroimmune interactions, as well as the development of excitotoxicity and damage to neurons in acute psychosis.

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Introduction. Alcohol abuse is more than 80% of cases of drug addiction in Russia, with 90% of alcoholics in working age - from 20 to 59 years. Alcohol dependence (AZ) is more often diagnosed in young patients under 30 years of age and leads to premature death of about half a million people annually. AZ leads to changes in systemic immunity and increased risk of infectious complications and severe organ damage. According to data of experimental and postmortem studies of AZ leads to neuroinflammation and disruption of the architectonics of the Central nervous system. Neuroimmune signal transmission is known to be critical for neuroplasticity regulation and is necessary for learning and memory [1, 2]. Excessive production of inflammatory mediators in the brain leads to damage to neurons. Chronic exposure to ethanol in mice increases levels of immune proteins CD14, TNF-α (tumor necrosis factor α), IL-1β (interleukin-1 beta), NF-kB p65, iNOS (inducible nitric oxide synthase), and COX-2 in the cortex, but these changes are not observed in mice knocked out by TLR4 [3]. It is suggested that immune signaling regulates alcohol consumption and that excessive alcohol consumption alters neuroimmune signaling by allowing positive feedback to increase consumption, cravings, and dependence [4, 5]. Objective: to study the level of systemic inflammation and changes in adaptive immunity in the early period after acute psychosis to assess their participation in the pathogenesis of alcoholic mental and cognitive disorders. Materials. The study included patients with stage 2 alcoholism with alcoholic psychosis (AP) - 28 people, 21 men and 7 women, mean age - 44.6 ± 4.1 years. The duration of AZ - 23.2 ± 6.3 years. Diagnosis (organic personality disorder And 07.8) installed in the hospitalization to the PCB 1. N. Alekseeva of Moscow. The exclusion criteria were acute infections, exacerbation of chronic infections, severe somatic pathology, viral hepatitis. The comparison group included 17 healthy volunteers 12 men, 5 wives, mean age 41.2 ± 6.5. Methods. Serum levels of IgA, IgM, IgG, CC (IL-1, IL-1RA, IL-2, IL-4, IL-8, IL-10, IFNy, TNFa), CRP and CIC were studied by ELISA. Phenotyping of the main lymphocyte subpopulations (CD3, CD4, CD8, CD16, CD19, CD45, CD56, CD38, HLA-DR, Treg) by flow cytometry (monoclonal at BD) was also performed. Results. The assessment of humoral immunity parameters revealed a significant increase in IgG levels in patients with alcohol dependence compared to the norm (1565 ± 114.32 and 1215 ± 95.12, respectively, p < 0.05). The content of IgA and IgM did not change in comparison with the norm and indicators of the control group. There was also a significant increase in CEC to 128 ± 13.40 at a rate of 79 ± 8.63 (p < 0.05). In the group of patients with alcohol dependence there was an increase in the main markers of systemic inflammatory response: the level of circulating immune complexes, C-reactive protein, cortisol, and proinflammatory cytokines IL-1β, IL-8 and TNFa (Table 1) compared with the control group and with normal values. In particular, the level of CRP was increased to 20.63 ± 7.3 mg/l, which was more than 10 times higher than the control values. Thus, in patients with CA after acute psychosis (delirium) activation of humoral immunity with impaired clearance of immune complexes was found. In addition, there was an increase in the content and activity of T-helpers, mainly of type 2 (with signs of insufficiency and dysfunction of Th1), a decrease in the content and activity of cytotoxicity system cells (EC, TNC and CTL) (figure1). Signs of systemic inflammation (increased CRP, cortisol, IL) were found. Conclusion. Activation of Th2 response and an excess of proinflammatory mediators in patients with AP through various ways of interaction with the Central nervous system (n. vagus, Horodnya plexus of the ventricles of the brain, and others) can participate in the disorders of metabolism of neurotransmitters in the Central nervous system involved in the pathogenesis of alcoholism, and in the maintenance of neuroinflammation. A high level of systemic inflammation can be both a trigger of psychosis and a manifestation of violations of neuroimmune interactions, as well as the development of excitotoxicity and damage to neurons in acute psychosis.

About the authors

N A Didkovsky

FSBI FCRC of Physical-Chemical Medicine FMBA of Russia, Moscow


I K Malashenkova

FSBI FCRC of Physical-Chemical Medicine FMBA of Russia, Moscow; NRC “Kurchatov Institute”, Moscow


D P Ogurtsov

FSBI FCRC of Physical-Chemical Medicine FMBA of Russia, Moscow; NRC “Kurchatov Institute”, Moscow


S A Krynskiy

NRC “Kurchatov Institute”, Moscow


N A Hailov

NRC “Kurchatov Institute”, Moscow


E I Chekulaeva

NRC “Kurchatov Institute”, Moscow


M V Mamoshina

NRC “Kurchatov Institute”, Moscow


V L Ushakov

NRC “Kurchatov Institute”, Moscow


N V Zakharova

Psychiatric Clinical Hospital No. 1 named after N.A. Alekseev, Moscow


G P Kostyuk

Psychiatric Clinical Hospital No. 1 named after N.A. Alekseev, Moscow


References

  1. Williamson LL, Bilbo SD. Chemokines and the hippocampus: A new perspective on hippocampal plasticity and vulnerability. Brain, Behavior, and Immunity. 2013;30:186-194. https://doi.org/10.1016/j.bbi.2013.01.077.
  2. Malashenkova IK, Krynskiy SA, Khailov NA, et al. The Role of Cytokines in Memory Consolidation. Biology Bulletin Reviews. 2016;6:126-140.
  3. Alfonso-Loeches S, Pascual-Lucas M, Blanco AM, et al. Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. The Journal of Neuroscience. 2010;30(24):8285-8295.
  4. Robinson G, Most D, Ferguson LB, et al. Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans. Int Rev Neurobiol. 2014;118:13-39.
  5. Kelley KW, Dantzer R. Alcoholism and Inflammation: Neuroimmunology of Behavioral and Mood ¬Disorders. Brain Behav Immun. 2011;25:13-20.

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Copyright (c) 2019 Didkovsky N.A., Malashenkova I.K., Ogurtsov D.P., Krynskiy S.A., Hailov N.A., Chekulaeva E.I., Mamoshina M.V., Ushakov V.L., Zakharova N.V., Kostyuk G.P.

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