Elsevier

Drug and Alcohol Dependence

Volume 163, 1 June 2016, Pages 77-83
Drug and Alcohol Dependence

Full length article
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

https://doi.org/10.1016/j.drugalcdep.2016.03.022Get rights and content

Highlights

Abstract

Background

The course of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) was investigated in alcohol-dependent individuals without liver disease in order to ascertain the use of these cytokines as markers for the follow-up testing and the outcome of the detoxification treatment.

Methods

Forty-eight alcohol-dependent individuals were admitted for alcohol detoxification. Blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4–5 weeks). Serum IL-7, IL-10 and G-CSF were measured with a commercially available sandwich enzyme immunoassay.

Results

IL-7 concentration was steadily high from admission up to two weeks later and then showed a fall, yet still remaining significantly higher than in the control group at the end of the detoxification treatment. IL-10 concentration was significantly low on admission, presenting a linear increase during therapy and remained insignificantly low at the end. G-CSF was significantly elevated on admission and presented a linear fall ending up in almost normal values at the end of the detoxification therapy.

Conclusions

The alterations in the concentration of IL-7, IL-10 and G-CSF and their trend to normalization during the detoxification therapy are indicative of the generalized immune system disorder, caused by alcohol abuse. Further studies will help in further elucidating the pathophysiology of the immune system function in alcohol abuse, while immunological parameters might serve as biological markers and diagnostic tools for the assessment of the course and the outcome of the detoxification therapy.

Introduction

Alcohol dependence represents a major social and medical issue worldwide, with severe adverse complications and consequences (WHO, 2014). Excessive drinking can lead to both reversible and permanent impairment of cognitive function and structural brain changes (Harper, 2009). Alcohol abuse impairs the immune response functions and increases the probability of the emergence of various cancer types, like colon, upper respiratory tract, liver and breast cancer (Dumitrescu and Shields, 2005, Kaphalia and Calhoun, 2013, Muralidharan et al., 2014, Oyesanmi et al., 2010, Stewart and Wild, 2014, Varela-Rey et al., 2013, Zhang et al., 2008).

In alcoholism, immunocompetent cells are affected in number, while the action of macrophages is seriously impaired (Baker and Jerrells, 1993, Morris et al., 2014, Szabo, 1999, Szabo and Mandrekar, 2002). Alcohol reduces the phagocytic activity of monocytes, macrophages, Kupffer cells, microglial cells and dendritic cells, as well as their ability to present antigens; processes that are necessary for the management of infections (Curtis et al., 2014, Curtis et al., 2013). Both chronic and acute alcohol exposure seems to contribute in immunomodulation through altering the differentiation and maturation process of monocyte-derived dendritic cells (Buttari et al., 2008). Alcohol impairs proliferation of hematopoietic stem cells, as well as their differentiation, especially in the granulocytic lineage (Melvan et al., 2012, Siggins et al., 2011, Smith et al., 2015, Zhang et al., 2009). It also impairs proliferation differentiation and normal function of lymphocytes (Malbergier et al., 2015, Parlet et al., 2014, Verma et al., 2008, Yue et al., 2012, Zhang et al., 2015).

Many immunological parameters, such as the tumor necrosis factor-alpha (TNF- a), interleukin (IL)-1β, IL-8, IL-12, IL-13, seem to be elevated in alcohol abuse or dependence, whereas IL-6 concentration decreases during detoxification treatment in alcohol dependence without liver disease (Achur et al., 2010, Chatzipanagiotou et al., 2010, Gonzalez-Quintela et al., 1999, Laso et al., 2007, Liappas et al., 2007, Nicolaou et al., 2004, Torrente et al., 2012).

There are no longitudinal studies about the course of IL-7, IL-10 and the Granulocyte Colony Stimulating Factor (G-CSF) during detoxification therapy, but only very few cross-sectional studies have been published about the concentrations of IL-10 and G-CSF in alcohol dependent individuals.

IL-7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons and epithelial cells (Krawczenko et al., 2005, Pillai et al., 2004, Sawa et al., 2009, Yu et al., 2014). IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells and stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and natural killer (NK) cells) (Clark et al., 2014, Faller et al., 2014, Klein Wolterink et al., 2010, Meazza et al., 2011, Reth and Nielsen, 2014, Silva et al., 2014). Its existence is important for the proliferation during certain stages of B cell maturation, T- and NK-cells survival, development and homeostasis (Clark et al., 2014, Dias et al., 2005, Tsapogas et al., 2011).

IL-10 is an anti-inflammatory cytokine with multiple, pleiotropic, effects in immunoregulation and inflammation (Porrini et al., 1995, Sanchez et al., 2015). It down regulates the expression of T helper-1 (Th1) cytokines, major histocompatibility complex (MHC) class II antigens, and co-stimulatory molecules on macrophages, though enhancing B cell survival, proliferation, and antibody production (Bona and Revillard, 2000, Cheng and Sharma, 2015, de Waal Malefyt et al., 1991, Deenick et al., 2013, Heine et al., 2014, Ingelsten et al., 2014, Oft, 2014, Perona-Wright et al., 2009, Rodgers et al., 2014, Striz et al., 2014, Wang et al., 2011).

The glycoprotein G-CSF, also known as colony-stimulating factor 3 (CSF 3), proliferates stimuli to the bone marrow for the production of granulocytes and stem cells while regulating their release into bloodstream. Along with the granulocyte colony-stimulating factor receptor (GCSFR), they form a complex which is part of the class I cytokine receptor signaling system, playing a major role in hematopoiesis during emergency conditions (inflammatory environment), malignancies and in the mobilization of hematopoietic progenitor cells (HPCs) during neutropenic conditions; therefore, these properties have been widely exploited by clinical medicine (Bendall and Bradstock, 2014, Holig, 2013, Liongue et al., 2009).

The aim of the present study was to investigate the course of these three cytokines, in order to ascertain their use as markers for the follow up and the outcome of the detoxification treatment in alcohol dependence.

Section snippets

Patient population

The sample of the study comprised 48 alcohol-dependent individuals without liver disease (40 males and 8 females), enrolled over a one-year period, who had consecutively contacted the Drug and Alcohol Addiction Clinic of the Aeginition University Hospital in Athens, Greece. The absence of liver disease was diagnosed after a thorough clinical investigation by a hepatologist. All patients fulfilled the DSM-IV diagnostic criteria for alcohol abuse/dependent-‘primary alcoholism’ (American

Patients and control group

The age in years (mean ± SD) for the control group was 43.35 ± 10.52 and for patients 46.42 ± 10.21 years. Although the age of the control group is slightly smaller than patients, it does not differ significantly (p = 0.068). The average daily amount of consumed alcohol was 332.07 ± 155.89 g/day (median = 294 g/day).

Routine laboratory examinations

A significant decline of ALT, AST and γGT values, which routinely serve as indices of the patient’s hepatic function, was observed; this is consistent with the usually expected outcome of the

Discussion

There is little information about the role of IL-7, IL-10 and G-CSF in clinical entities associated with immunosuppression, such as chronic alcohol abuse. Alcohol is a modulator of host defense, causing impaired immunity at the level of innate and acquired immune responses (MacGregor and Louria, 1997, Szabo, 1999). The effect of alcohol abuse also influences the various cytokine pathways in favor of pro-inflammatory cytokine production in macrophages and monocytes, causing a strong generalized

Funding source

Nothing declared.

Contributors

All authors have read and approved the manuscript for submission to “Drug and Alcohol Dependence”, have made a substantial contribution to the conception, design, gathering, analysis and/or interpretation of data and a contribution to the writing and intellectual content of the article; and acknowledge that they have exercised due care in ensuring the integrity of the work.

Conflict of interest

The authors declare that there are no conflicts of interest.

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