Institute for Regeneration and Repair, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK.
Service of Immunology and Allergy, Center of Human Immunology Lausanne, Department of Medicine and Department of Laboratory Medicine and Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Lancet Respir Med. 2024 Apr;12(4):323-336. doi: 10.1016/S2213-2600(23)00468-X. Epub 2024 Feb 23.
Sepsis is a common and deadly condition. Within the current model of sepsis immunobiology, the framing of dysregulated host immune responses into proinflammatory and immunosuppressive responses for the testing of novel treatments has not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalised immunomodulation. In this Personal View, we highlight that many fundamental immunological concepts such as resistance, disease tolerance, resilience, resolution, and repair are not incorporated into the current sepsis immunobiology model. The focus for addressing heterogeneity in sepsis should be broadened beyond subtyping to encompass the identification of deterministic molecular networks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as altered homoeostasis with pathological disruption of immune-driven resistance, disease tolerance, resilience, and resolution mechanisms. Our proposal highlights opportunities to identify novel treatment targets and could enable successful immunomodulation in the future.
脓毒症是一种常见且致命的病症。在当前的脓毒症免疫生物学模型中，将失调的宿主免疫反应框定为促炎和免疫抑制反应，以测试新的治疗方法，但并没有产生成功的免疫调节疗法。因此，最近的重点是将可观察到的异质性解析为脓毒症的亚型，以实现个性化的免疫调节。在本个人观点中，我们强调，许多基本的免疫学概念，如抵抗、疾病耐受、弹性、解决和修复，并没有被纳入当前的脓毒症免疫生物学模型。解决脓毒症异质性的重点应该超越亚型，包括确定确定性分子网络或主导机制。我们明确地将脓毒症中失调的宿主免疫反应重新定义为免疫驱动的抵抗、疾病耐受、弹性和解决机制的病理性破坏的改变的体内平衡。我们的建议突出了识别新的治疗靶点的机会，并可能在未来实现成功的免疫调节。
