Ru-Band Lu1, Tzu-Yun Wang2, Sheng-Yu Lee3, Shiou-Lan Chen4, Yun-Hsuan Chang5, Po See Chen6, Shih-Hsien Lin7, Chun-Hsien Chu8, San-Yuan Huang9, Nian-Sheng Tzeng10, I Hui Lee6, Kao Chin Chen6, Yen Kuang Yang11, Ping Chen12, Shih-Heng Chen13, Jau-Shyong Hong13. 1. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Addiction Research Center, National Cheng Kung University, No.1, University Road, Tainan 70101, Taiwan; The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou City Sheng Jin Road No. 1 Huanglong residential area, China; Beijing YiNing Hospital, No.9 Minzhuang Road, Haidian District, Beijing 100195, China; Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan. 2. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. Electronic address: wangty@mail.ncku.edu.tw. 3. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung 81362, Taiwan. 4. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan; Lipid Science and Aging Research Center, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan. 5. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Department of Psychology, Asia University, 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan. 6. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Addiction Research Center, National Cheng Kung University, No.1, University Road, Tainan 70101, Taiwan. 7. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan. 8. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, 3F, No.367, Sheng-Li Rd., North District, Tainan 70456, Taiwan. 9. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec.2, Chenggong Rd., Neihu District, Taipei 11490, Taiwan. 10. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec.2, Chenggong Rd., Neihu District, Taipei 11490, Taiwan; Student Counseling Center, National Defense Medical Center, No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei 11490, Taiwan. 11. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan; Addiction Research Center, National Cheng Kung University, No.1, University Road, Tainan 70101, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, No.345, Zhuangjing Rd., Douliu, Yunlin 64043, Taiwan. 12. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA. 13. Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, 111 T.W. Alexander Drive, N.C. 27709, USA.
Abstract
BACKGROUND: The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients. METHOD: We investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes. RESULTS: We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive (+) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes. CONCLUSION: Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted.
BACKGROUND: The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUDpatients. METHOD: We investigated OUDpatients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, transforming growth factor (TGF)-β1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes. RESULTS: We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-β1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive (+) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes. CONCLUSION: Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUDpatients might be warranted.
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