Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- & Behavioral Sciences, University Hospital Essen, 45147, Essen, Germany.
iC42 Clinical Research and Development, Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Neuroimmune Pharmacol. 2024 May 11;19(1):18. doi: 10.1007/s11481-024-10122-0.
Suppression of immune functions can be elicited by behavioural conditioning using drugs such as cyclosporin A or rapamycin. Nevertheless, little is known about the underlying mechanisms and generalisability of this phenomenon. Against this background, the present study investigated whether the pharmacological properties of fingolimod (FTY720), an immunosuppressive drug widely applied to treat multiple sclerosis, can be conditioned in rats by means of taste-immune associative learning. For this purpose, a conditioned taste avoidance paradigm was used, pairing the presentation of a novel sweet drinking solution (saccharin or sucrose) as conditioned stimulus (CS) with therapeutically effective doses of FTY720 as unconditioned stimulus (US). Subsequent re-exposure to the CS at a later time point revealed that conditioning with FTY720 induced a mild conditioned taste avoidance only when saccharin was employed as CS. However, on an immunological level, neither re-exposure with saccharin nor sucrose altered blood immune cell subsets or splenic cytokine production. Despite the fact that intraperitonally administered FTY720 could be detected in brain regions known to mediate neuro-immune interactions, the present findings show that the physiological action of FTY720 is not inducible by mere taste-immune associative learning. Whether conditioning generalises across all small-molecule drugs with immunosuppressive properties still needs to be investigated with modified paradigms probably using distinct sensory CS. Moreover, these findings emphasize the need to further investigate the underlying mechanisms of conditioned immunomodulation to assess the generalisability and usability of associative learning protocols as supportive therapies in clinical contexts.
使用环孢素 A 或雷帕霉素等药物进行行为条件作用可以抑制免疫功能。然而，对于这种现象的潜在机制和普遍性知之甚少。在此背景下，本研究探讨了免疫抑制药物芬戈莫德（FTY720）的药理学特性是否可以通过味觉-免疫联想学习在大鼠中进行条件作用。为此，使用条件味觉回避范式，将新的甜味饮用溶液（糖精或蔗糖）作为条件刺激（CS）与 FTY720 的治疗有效剂量作为非条件刺激（US）配对。随后在稍后的时间点重新暴露于 CS 时，发现 FTY720 条件作用仅在使用糖精作为 CS 时才会引起轻度条件味觉回避。然而，在免疫学水平上，无论是重新暴露于糖精还是蔗糖，都不会改变血液免疫细胞亚群或脾细胞因子的产生。尽管腹腔内给予的 FTY720 可以在已知介导神经-免疫相互作用的脑区中检测到，但本研究结果表明，FTY720 的生理作用不能通过单纯的味觉-免疫联想学习来诱导。具有免疫抑制特性的所有小分子药物的条件作用是否普遍存在，仍需要使用可能使用不同感觉 CS 的改良范式进行调查。此外，这些发现强调需要进一步研究条件免疫调节的潜在机制，以评估联想学习方案作为临床环境中的支持性治疗的普遍性和可用性。
