Salem Yasmin, Leisengang Stephan, Jakobs Marie, Dombrowski Kirsten, Bihorac Julia, Heiss-Lückemann Laura, Wenzlaff Sebastian, Trautmann Lisa, Hagernacker Tim, Schedlowski Manfred, Hadamitzky Martin
Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- Behavioral Sciences (C-TNBS), University Hospital Essen, Essen, Germany.
Department of Neurology, Center for Translational Neuro-Behavioral Sciences (C- TNBS), University Hospital Essen, Essen, Germany.
Sci Rep. 2025 Aug 12;15(1):29456. doi: 10.1038/s41598-025-13850-2.
Taste-immune associative learning has been shown to mimic immunopharmacological responses. Conditioned pharmacological effects may therefore be considered as controlled drug dose reduction strategy to maintain treatment efficacy. Against this background, the present study applied an established taste-immune associative learning protocol to a rat model of DNFB-induced contact hypersensitivity. After repeated pairings of a saccharin taste (conditioned stimulus, CS) with injections of the immunosuppressant cyclosporine A (CsA, unconditioned stimulus, UCS), animals were sensitized with the hapten. Retrieval started by presenting the CS together with sub-effective doses of CsA. This procedure preserved a conditioned suppression of splenic cytokine production. Compared to full dose treated animals, conditioned effects were neither observed in draining lymph nodes nor did it prevent ear swelling. These findings suggest that active sensitization might have masked a potential conditioned reduction of local allergic reactions. Additionally, symptoms such as itch may be more suited as readout parameter since it better reflects patients' disease burden. The present study reaffirms that learned immunopharmacological effects can be preserved using a memory-updating approach. It also emphasizes the need to further explore the usability of associative learning protocols in clinical contexts in order to address disease-specific symptoms more effectively.
味觉-免疫联想学习已被证明可模拟免疫药理学反应。因此，条件性药理作用可被视为一种可控的药物剂量减少策略，以维持治疗效果。在此背景下，本研究将一种既定的味觉-免疫联想学习方案应用于二硝基氟苯（DNFB）诱导的接触性超敏反应大鼠模型。在将糖精味觉（条件刺激，CS）与注射免疫抑制剂环孢素A（CsA，非条件刺激，UCS）反复配对后，用半抗原使动物致敏。通过将CS与亚有效剂量的CsA一起呈现来启动检索。该程序保留了对脾脏细胞因子产生的条件性抑制。与全剂量治疗的动物相比，在引流淋巴结中未观察到条件性效应，也未预防耳部肿胀。这些发现表明，主动致敏可能掩盖了局部过敏反应潜在的条件性减轻。此外，瘙痒等症状可能更适合作为读出参数，因为它能更好地反映患者的疾病负担。本研究再次证实，使用记忆更新方法可以保留习得的免疫药理作用。它还强调需要进一步探索联想学习方案在临床环境中的可用性，以便更有效地解决特定疾病的症状。
