Schmidt Justine, Reinold Johanna, Rohn Hana, Schedlowski Manfred, Engler Harald, Elsenbruch Sigrid, Benson Sven
Institute for Medical Education, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Institute of Medical Psychology and Behavioral Immunobiology, C-TNBS, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
BMC Med. 2025 Aug 4;23(1):455. doi: 10.1186/s12916-025-04292-8.
Systemic inflammation triggers a wide range of sickness symptoms, including bodily discomfort and affective symptoms, which are relevant to numerous health conditions. While extensive research in the placebo field demonstrates that positive expectations can improve symptoms, it remains unclear if interventions designed to augment positive treatment expectations can alleviate sickness symptoms in the context of immunomodulatory drug therapies.
In this randomized, controlled, fully balanced 2 × 2 factorial placebo design, N = 124 healthy volunteers received either active ibuprofen treatment (600 mg per os) or placebo, combined with either a positive or neutral labeling of the treatment by the physician. All participants were intravenously injected with lipopolysaccharide (LPS, 0.8 ng per kg of body weight) as a translational model of inflammation-induced sickness symptoms. Primary outcomes were bodily and affective symptoms, assessed at baseline and up to 6 h after injection, along with a range of inflammatory markers.
Ibuprofen substantially alleviated inflammation-induced symptoms. Positive labeling also improved bodily and affective symptoms of sickness, even in placebo-treated groups. Notably, positive labeling enhanced ibuprofen's efficacy for alleviating affective symptoms, supporting that expectations can boost the efficacy of a highly effective anti-inflammatory treatment. However, labeling did not influence changes in physiological markers of inflammation, suggesting that the effects of expectations primarily act through mechanisms distinct from direct modulation of peripheral immune responses.
Placebo mechanisms engaged by physician communication can independently alleviate inflammation-induced symptom burden and enhance the efficacy of an anti-inflammatory medication. Results underscore the critical role of healthcare provider communication and pave the way for improved treatment strategies for conditions characterized by inflammation-driven symptoms.
DRKS00023088, registration website German Clinical Trials Register (date registered: 10/22/2020).
全身性炎症会引发一系列疾病症状，包括身体不适和情感症状，这些症状与多种健康状况相关。虽然安慰剂领域的大量研究表明积极期望可以改善症状，但在免疫调节药物治疗背景下，旨在增强积极治疗期望的干预措施是否能减轻疾病症状仍不清楚。
在这项随机、对照、完全平衡的2×2析因安慰剂设计中，124名健康志愿者接受了活性布洛芬治疗（口服600毫克）或安慰剂，并结合医生对治疗的积极或中性标签。所有参与者静脉注射脂多糖（LPS，每公斤体重0.8纳克）作为炎症诱导疾病症状的转化模型。主要结局是在基线时以及注射后长达6小时评估的身体和情感症状，以及一系列炎症标志物。
布洛芬显著减轻了炎症诱导的症状。积极标签也改善了疾病的身体和情感症状，即使在安慰剂治疗组中也是如此。值得注意的是，积极标签增强了布洛芬减轻情感症状的疗效，支持了期望可以提高高效抗炎治疗的疗效。然而，标签并未影响炎症生理标志物的变化，这表明期望的作用主要通过不同于直接调节外周免疫反应的机制发挥作用。
医生沟通引发的安慰剂机制可以独立减轻炎症诱导的症状负担，并增强抗炎药物的疗效。结果强调了医疗服务提供者沟通的关键作用，并为改善以炎症驱动症状为特征的疾病的治疗策略铺平了道路。
DRKS00023088，注册网站德国临床试验注册中心（注册日期：2020年10月22日）。
