Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments

Ann Manzardo,Elizabeth Penick,Albert Poje,Merlin Butler

doi:10.3390/ijms17040472

Abstract

Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33–58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40–58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p < 0.05). Elevated inflammatory mediators in alcoholism may influence brain function leading to increased impulsiveness and/or phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention.

Highlights

Alcoholism is a complex, multifactorial behavioral disorder characterized by the loss of control over alcohol consumption often involving other drug abuse with a relapsing and remitting course leading to clinically significant impairment [1]
The resulting biochemical disturbances are known to trigger an enhanced inflammatory cascade involving the production of reactive oxygen species by activated macrophages and increased cytokine production by Kupffer cells in the liver and other tissues [3,4,5,12,13]
Plasma levels of 14 hematopoietin-derived cytokines (interleukin 1α (IL1α); interleukin 1β (IL1β); interleukin 1 receptor antagonist (IL1Ra); interleukin 2 (IL2); interleukin 3 (IL3); interleukin 4 (IL4); interleukin 5 (IL5); interleukin 6 (IL6); interleukin 9 (IL9); interleukin 10 (IL10); interleukin 13 (IL13); interleukin 15 (IL15); interleukin 12 subunit p40 (IL12(p40)); Fit3Ligand), 2 inflammatory cytokines (macrophage inflammatory protein 1 α (MIP1α); transforming growth factor α (TGFα)) and TNFβ fell below detection limits in >2/3 of subjects and were excluded from primary analysis of cytokine levels

Summary

Introduction

Alcoholism is a complex, multifactorial behavioral disorder characterized by the loss of control over alcohol consumption often involving other drug abuse with a relapsing and remitting course leading to clinically significant impairment [1]. Direct and indirect effects of high levels of alcohol consumption have pervasive effects on multiple organ systems including the liver, gastrointestinal tract and bone, as well as brain, endocrine and other systems [2,3,4,5]. These effects are well-characterized and include alteration of cellular functioning, metabolism and energy production, impaired protein and nucleic acid synthesis, disruption of hormone regulation and function, as well as impaired absorption and transport of essential nutrients [3,4,5,6,7,8,9,10,11]. T helper-2 (Th2) derived cytokines (e.g., interleukin 4 (IL4); interleukin 10 (IL10)) are considered anti-inflammatory and generally inhibit cytokine release [16]

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Conclusion