Kyzer Jillian L, McGuire Mason, Park Hyeri, Belz Tyson F, Bonakdar Robert, Janda Kim D, Wenthur Cody J
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, United States.
Department of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, California 92037, United States.
ACS Pharmacol Transl Sci. 2020 Aug 25;3(5):896-906. doi: 10.1021/acsptsci.0c00057. eCollection 2020 Oct 9.
In addition to the risk of developing opioid use disorder (OUD), known side-effects of long-term opioid use include chronic inflammation and hyperalgesia, which may arise from immune responses induced following chronic opioid use. To investigate this hypothesis, blood samples were obtained from individuals with chronic back pain who were either chronically taking prescription opioids or had minimal recent opioid exposure. Patient samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) against hydrocodone- or oxycodone-hapten conjugates to assess the levels of antibodies present in the samples. While no specific response was seen in opioid-naïve subjects, we observed varying levels of anti-opioid IgM antibodies in the exposed subjects. In these subjects, antibody formation was found to be weakly correlated with current reported daily opioid dose. Other drugs of abuse found to elicit an immune response have been shown to generate advanced glycation end-products (AGEs) through reaction with glucose and subsequent modification of self-proteins. Investigations into this potential mechanism of anti-opioid antibody production identified reduced the formation of reactive intermediate species upon norhydrocodone reaction with glucose in comparison with nornicotine, thus identifying potentially important differences in hapten processing to yield the observed adaptive immune response.
除了有发展为阿片类药物使用障碍（OUD）的风险外，长期使用阿片类药物的已知副作用还包括慢性炎症和痛觉过敏，这可能源于长期使用阿片类药物后引发的免疫反应。为了研究这一假设，从患有慢性背痛的个体中采集血样，这些个体要么长期服用处方阿片类药物，要么近期很少接触阿片类药物。使用针对氢可酮或羟考酮半抗原缀合物的酶联免疫吸附测定（ELISA）分析患者样本，以评估样本中存在的抗体水平。在未接触过阿片类药物的受试者中未观察到特异性反应，但我们在接触过阿片类药物的受试者中观察到了不同水平的抗阿片类IgM抗体。在这些受试者中，发现抗体形成与当前报告的每日阿片类药物剂量呈弱相关。已发现其他引起免疫反应的滥用药物可通过与葡萄糖反应并随后修饰自身蛋白质产生晚期糖基化终产物（AGEs）。对这种抗阿片类抗体产生的潜在机制的研究表明，与去甲烟碱相比，去氢可酮与葡萄糖反应时反应性中间物种的形成减少，从而确定了在产生观察到的适应性免疫反应的半抗原加工过程中潜在的重要差异。
