Abstract
Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.
Highlights
An estimated 40 million people with substance-use disorders (SUDs) require addiction treatment services, accounting for approximately 0.6 million drug-related deaths each year [1]
In the present study, using luminex human magnetic assay and high-throughput sequencing technologies, we report the short-term and long-term alterations of circulating cytokines and Ex-long non-coding RNA (lncRNA)/mRNAs in heroin addicts during substance withdrawal
After controlling for various factors, we successfully identified a set of critical lncRNAs and mRNAs in circulating exosomes associated with Th1/Th2/Th17 cytokine balance and switch in heroin addicts
Summary
An estimated 40 million people with substance-use disorders (SUDs) require addiction treatment services, accounting for approximately 0.6 million drug-related deaths each year [1]. Heroin remains one of the most abused illegal drugs in China. It is associated with a wide range of deleterious health problems and harmful economic consequences to individuals and communities [2]. The administration of heroin suppresses some of the central nervous system (CNS) functioning, including heart rate, breathing, and blood pressure. The withdrawal effects are usually the opposite of the suppressive effects. Instead of euphoria, reduced heart rate, and sedation, heroin addicts may experience irritable mood, anxiety, and rapid heart rate [3]
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