Abstinent patients with alcohol use disorders show an altered plasma cytokine profile: Identification of both interleukin 6 and interleukin 17A as potential biomarkers of consumption and comorbid liver and pancreatic diseases.

BACKGROUND: Recent studies have demonstrated that alcohol consumption can modulate the immune system by directly activating natural immunity and triggering inflammatory processes in the central nervous system and in peripheral organs, such as the liver and pancreas. Patients with alcohol use disorders have an elevated frequency of comorbid mental disorders and gut diseases (i.e. fatty liver and pancreatitis) that complicate diagnosis, treatment and prognosis. AIMS: The present study aims to explore possible associations in circulating plasma cytokine concentrations in abstinent patients diagnosed with alcohol use disorders. METHODS: To this end, 85 abstinent subjects with alcohol use disorders from an outpatient setting and 55 healthy subjects were evaluated for both substance and mental disorders. The plasma levels of cytokines interleukin 1 beta, interleukin 4, interleukin 6, interleukin 17A, interferon gamma and tumour necrosis alpha were determined and their association with (a) history of alcohol consumption, (b) psychiatric comorbidity and (c) liver/pancreas comorbidities was explored. RESULTS: We found that plasma concentrations of interleukin 1 beta, interleukin 6 and tumour necrosis alpha were increased, whereas plasma concentrations of interleukin 4, interleukin 17A and interferon gamma were decreased in abstinent alcohol use disorder patients as compared with control subjects. Moreover, we found that changes in interleukin 6 and interleukin 17A plasma concentrations in alcohol use disorder patients were associated with the presence of liver and pancreatic diseases. CONCLUSION: The present results suggest alcohol use disorder is associated with alterations of plasma cytokines, being interleukin 6 and interleukin 17A potential biomarkers of the presence of comorbidities of digestive organs. The clinical relevance of these findings is discussed in the context of alcohol-induced inflammatory processes.

Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders.

The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis.

BACKGROUND: Cocaine use disorder (CUD) is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation. METHODS: The study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain). The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group) and matched control subjects (N = 81, control group). Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNγ), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-17α (IL-17α), macrophage inflammatory protein 1α (MIP-1α) and transforming growth factor α (TGFα) levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables. RESULTS: While 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients displayed greater cocaine symptom severity when they were diagnosed with psychiatric comorbidity. Regarding inflammatory factors, we observed significantly lower plasma levels of IL-17α (p < 0.001), MIP-1α (p < 0.001) and TGFα (p < 0.05) in the cocaine group compared with the levels in the control group. Finally, there was a significant primary effect of dual diagnosis on the plasma concentrations of TGFα (p < 0.05) in the cocaine group, and these levels were lower in patients with dual diagnoses. DISCUSSION: IL-17α, MIP-1α and TGFα levels are different between the cocaine and control groups, and TGFα levels facilitate the identification of patients with dual diagnosis. Because TGFα reduction is associated with enhanced responses to cocaine in preclinical models, we propose TGFα as a potential biomarker of complex CUD in humans.