Supplementary Material for: Effectiveness of Stress-Reducing Interventions on the Response to Challenges to the Immune System: A Meta-Analytic Review

Background: There is consistent evidence showing an interplay between psychological processes and immune function in health and disease processes. Objectives: The present systematic review and meta-analysis aims to provide a concise overview of the effectiveness of stress-reducing psychological interventions on the activation of immune responses in both healthy subjects and patients. Methods: Included are 3 types of challenges: in vivo, in vitro, and psychophysiological. Such challenges are designed to mimic naturally occurring immune-related threats. Results: A systematic literature search was conducted using PubMed, EMBASE, and PsychInfo, resulting in 75 eligible studies. The risk of bias was assessed with the Cochrane risk-of-bias tool. Across all studies, a small-to-medium effect size was found for the effects of psychological interventions on optimization of the immune function (g = 0.33; 95% CI 0.22–0.43). While the largest effects were found for in vivo immune-related challenges (g = 0.61; 95% CI 0.34–0.88; especially on studies that incorporated skin tests and wound healing), studies incorporating psychophysiological challenges and in vitro immune-related stimulations similarly suggest more optimal immune responses among those receiving stress-reducing interventions (g = 0.28; 95% CI 0.15–0.42). Conclusion: These findings showed substantial heterogeneity depending on the type of challenge, the study populations, and the intervention types. These data demonstrate support for the effectiveness of stress-reducing psychological interventions in improving immunity in studies that tested immune function by means of incorporating an in vivo,in vitro, or psychophysiological challenge. Future research should more consistently incorporate challenges into the study design to gather more insights in the mechanisms underlying the optimized immune function following a psychological intervention. This is also relevant for clinical practice, as psychological interventions can possibly supplement, or at least partially replace, current drug treatments in various somatic conditions to reduce side effects.背景：已有一致的研究证据表明，在健康与疾病进程中，心理活动与免疫功能之间存在相互作用。 目的：本项系统评价与荟萃分析旨在简要概述减压心理干预对健康受试者与患者群体免疫应答激活的效果。 方法：本研究纳入三类免疫挑战模型：体内（in vivo）、体外（in vitro）以及心理生理学模型，此类模型均旨在模拟自然发生的免疫相关威胁刺激。 结果：本研究通过PubMed、EMBASE及PsycInfo开展系统性文献检索，最终纳入75项符合纳入标准的研究。采用Cochrane偏倚风险评估工具对研究偏倚风险进行评价。综合所有研究来看，减压心理干预对免疫功能优化的效应量为小至中等水平（g = 0.33；95%置信区间CI：0.22–0.43）。其中体内免疫相关挑战模型的效应最为显著（g = 0.61；95%CI：0.34–0.88），尤其在纳入皮肤试验与伤口愈合相关指标的研究中表现突出；而采用心理生理学挑战模型与体外免疫刺激模型的研究同样显示，接受减压心理干预的群体免疫应答更优（g = 0.28；95%CI：0.15–0.42）。 结论：本研究结果显示，研究异质性主要取决于免疫挑战模型类型、研究人群以及干预手段类型。上述数据证实，在通过体内、体外或心理生理学挑战模型检测免疫功能的研究中，减压心理干预可有效改善机体免疫功能。未来研究应在试验设计中更统一地纳入免疫挑战模型，以进一步阐明心理干预后免疫功能优化的潜在机制。该研究结果对临床实践同样具有参考价值：针对多种躯体疾病，心理干预或可补充现有药物治疗方案，或至少可部分替代现行药物治疗，从而降低不良反应发生风险。