Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and
Zunyue Zhang1,2, Hongjin Wu1,2, Qingyan Peng1,2
1National Health Commission (NHC) Key Laboratory of Drug Addiction Medicine (Kunming Medical University), The First Affiliated Hospital of Kunming Medical University, Kunming, China.
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.
Insights
Heroin withdrawal disrupts immune balance, altering T-helper cell responses and cytokine profiles. While some immune markers normalize in protracted withdrawal, others remain dysregulated, impacting heroin addiction pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Neuroscience
Background:
- Heroin addiction and withdrawal significantly impact physiological functions, notably immune responses.
- The precise molecular mechanisms underlying these immune alterations during heroin withdrawal remain largely unknown.
Purpose of the Study:
- To investigate the molecular inflammatory interactome, focusing on cytokines and transcriptome regulatory networks in heroin addicts during acute and protracted withdrawal.
- To compare these molecular profiles with those of healthy controls.
Main Methods:
- Simultaneously assessed 27 cytokines in 41 heroin addicts (20 acute withdrawal, 21 protracted withdrawal) and 38 healthy controls.
- Profiled exosomal long non-coding RNA (lncRNA) and mRNA from plasma.
- Constructed co-expression gene regulation networks to identify lncRNA-mRNA-pathway associations.
Main Results:
- Acute withdrawal showed disturbed T-helper (Th)1/Th2, Th1/Th17, and Th2/Th17 balances, with reduced IL-2 and elevated IL-4, IL-10, IL-17A.
- These imbalances largely normalized by the protracted withdrawal stage, though TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated.
- Identified specific lncRNA-mRNA-pathway pairs linked to altered cytokine profiles and Th imbalances.
Conclusions:
- Heroin withdrawal induces significant, stage-dependent alterations in immune cell balance and cytokine expression.
- Exosomal lncRNA and mRNA networks are associated with these immune dysregulations.
- Findings provide a basis for understanding withdrawal pathophysiology and potential therapeutic targets.
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