The Effects of Alcoholism Pharmacotherapy on Immune Responses in Alcohol-Dependent Patients

Abstract

Chronic alcohol use has profound modulatory effects on the immune system. Both the innate and the acquired immunity are compromised. The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission. Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services. In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics. Six groups were studied. Group A included 10 patients who were still using alcohol. Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy. Groups C, D and E were composed of 10 patients each, treated for at least 6 months with oral doses of gamma hydroxybutiric acid, naltrexone or disulfiram respectively. Ten age- and sex-matched healthy volunteers who never misused alcohol were included as a control group. Lymphoproliferation and peripheral mononuclear cell production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokines IL-1 and TNF-alpha were evaluated in all the patients and controls. The level of activity of the hypothalamus pituitary adrenal axis was assessed. Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment. In this group a significant alteration of cytokine production was observed. TNF and IFN-gamma were lower than controls, while the Th2 cytokine IL-4 was increased. These altered levels state for a Th1/Th2 unbalance characterized by decreased Th1 response in the presence of Th2 predominance. In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered. These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients.

Changes in Tumor Necrosis Factor-α, Heat Shock Protein 70, Malondialdehyde, and Superoxide Dismutase in Patients With Different Severities of Alcoholic Fatty Liver Disease

“…In one study, proinflammatory cytokine TNF-α levels, lymphoproliferation, and peripheral mononuclear cell production of the Th1 cytokine IFN-γ decreased as Th2 cytokine IL4 levels increased, which consequently altered the Th1/Th2 equilibrium. 26 Another study demonstrated that stimulated Kupffer cells induced oxidative stress and produced proinflammatory cytokines (eg, TNF-α), which resulted in hepatocellular damage. 16 However, these data support a mechanism that may rely on ethanol synergizing with LPS to upregulate the induction of TNF gene expression and TNF overproduction by decreasing cellular cAMP levels in monocytes/macrophages.…”

Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice

“…In human opiate addicts, the level of TNF-α expression in the brain (locus coeruleus) is higher than that in control subjects (Dyuizen and Lamash 2009). Levels of circulating TNF-α are altered in alcoholics, opiate addicts, and cocaine or marijuana abusers (Baldwin et al 1997;Peng et al 1999;Irwin et al 2007Irwin et al , 2009Gonzalez-Quintela et al 2008;Sacerdote et al 2008;Li et al 2009;Franchi et al 2010), and TNF-α may be a candidate biomarker of alcohol abuse and alcoholism (Achur et al 2010). In our study in animal, TNF-α (−/−) mice were more sensitive to METH self-administration and had a higher motivation for getting METH than wild-type mice.…”

“…Yet reports of the level of circulating TNF-α in human alcoholics, opiate addicts, and cocaine or marijuana abusers are not consistent. Some reports show that the level increases (Gonzalez-Quintela et al 2008;Peng et al 1999;Irwin et al 2009), and others show that the level decreases or does not change (Baldwin et al 1997;Irwin et al 2007;Sacerdote et al 2008;Li et al 2009;Franchi et al 2010). In animals, repeated administration of psychostimulants or opiates induced TNF-α production in the brain or immune system (Friedman and Eisenstein 2004;Nakajima et al 2004;Niwa et al 2007a; Kubera et al 2008).…”

Disulfiram

“…A study of 5 groups with alcohol dependence by Franchi et al 36 concluded that pharmacotherapy may ameliorate the immune system in alcoholic patients more than with group therapy (Table 6). …”