Dynamics and Correlation of Multiplex Immune Profiling Reveal Persistent Immune Inflammation In Drug Users After Withdrawal

Background: Drug withdrawal elicits immune responses contributing to the development of withdrawal symptoms and relapse. The understanding of the immunologic dynamics after drug withdrawal is limited, precluding the finding of promising immune intervention measures. Methods: We performed cytokine and multiplex immune profiling in drug users after withdrawal and identified the correlation between 27 cytokines and other immune parameters. Findings: We showed that broad and strong inflammatory responses occurred at the early stage after drug withdrawal, and the inflammatory responses showed a downtrend with the extension of withdrawal time. Notably, immune dysregulation still exists and may last longer in heroin and METH users after withdrawal for 12 months. IL-7 may play an important role in regulating the immune responses after drug withdrawal. Moreover, after withdrawal within 15 days, the Th1 cytokine (IL-2) was decreased markedly, but the Th2 cytokines (IL-4, IL-6 and IL-10) increased significantly compared with healthy controls in heroin users. Interpretation: Our findings suggest the cytokines, immune cells, complement and immunoglobulin form a complex immune network in regulating immune responses after withdrawal, which indicates immunotherapy as a promising immune intervention measure for drug relapse. Funding: Funded by the National Natural Science Foundation of China (81660094, 32060177), the Fund for Yunling Scholar (YLXL20170002) and the General Joint Project of the Department of Science and Technology of Yunnan Province and Kunming Medical University (2017FE467(-038), 2017FE467(-130)) etc. Declaration of Interest: The authors declare no competing interests. Ethical Approval: All methods and recruitment procedures described were approved by the Research Ethics Committee of the First Affiliated Hospital of Kunming Medical University (No. 2018 Lunshen L42)