Understanding sepsis-induced immunosuppression and organ dysfunctions: from immunosuppression to immunotherapy

D. Gupta, T. Sinha, Richa Pathak, S. Bhoi, D. Rao
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Abstract

Sepsis is a life-threatening condition caused by dysregulated host immune response to infection, leading to persistent inflammation followed by immunosuppression. Sepsis represents a substantial global health problem owing to protracted inflammation, immune suppression, and susceptibility to nosocomial infections. Despite continuing progress in the development of antibiotics, fluid resuscitation, and other supportive care therapies, no specific immunomodulatory drugs or immunotherapeutic adjuncts for the treatment of sepsis are available to date. The advances in tertiary care facilities and patient care have improved the survival of sepsis patients in the initial hyper-inflammatory phase of sepsis. However, the majority of sepsis patients succumb later due to prolong immunosuppression. The sepsis-induced immune dysregulation and its long-term effects on mortality are under meticulous investigations that are still poorly defined. Sepsis leads to the impaired functions of the innate and adaptive immune systems. The exhaustion of T cells, reduced expression of human leukocytes antigen (HLA)-DR on monocytes, and induced uncontrolled apoptosis of immune cells have been reported as hallmark features of sepsis. Sepsis-induced immune cell apoptosis of immune cells is a primary contributing factor to the immunosuppression in sepsis. Preclinical studies have identified several new therapeutic targets for therapy in sepsis, including monoclonal antibodies (Abs) and anti-apoptotic agents to reduce T cells exhaustion, immune cells apoptosis, and restoring immune cells functions. Recent studies have centered on immune-modulatory therapy. The review article will focus solely on sepsis’ effects on innate and adaptive cells functions that contribute to immunosuppression. Finally, it is discussed how immune cells responsible for immunosuppression might be directly targeted to provide potential therapeutic benefits in treating sepsis and improving long-term survival.
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了解败血症诱导的免疫抑制和器官功能障碍:从免疫抑制到免疫治疗
脓毒症是一种危及生命的疾病,由宿主对感染的免疫反应失调引起,导致持续的炎症,随后是免疫抑制。脓毒症是一个严重的全球性健康问题,原因是长期炎症、免疫抑制和对医院感染的易感性。尽管抗生素、液体复苏和其他支持性护理疗法的发展不断取得进展,但迄今为止还没有用于治疗败血症的特异性免疫调节药物或免疫治疗辅助药物。三级医疗设施和患者护理的进步提高了脓毒症患者在脓毒症初始高炎症期的生存率。然而,大多数败血症患者由于免疫抑制延长而死亡。败血症引起的免疫失调及其对死亡率的长期影响正在进行细致的研究,但仍然没有明确的定义。脓毒症导致先天和适应性免疫系统功能受损。T细胞的衰竭,单核细胞上人类白细胞抗原(HLA)-DR的表达减少,以及诱导免疫细胞不受控制的凋亡已被报道为败血症的标志特征。脓毒症诱导的免疫细胞凋亡是脓毒症免疫抑制的主要因素。临床前研究已经确定了几种新的败血症治疗靶点,包括单克隆抗体(Abs)和抗凋亡药物,以减少T细胞衰竭,免疫细胞凋亡,恢复免疫细胞功能。最近的研究集中在免疫调节疗法上。这篇综述文章将只关注脓毒症对先天和适应性细胞功能的影响,这些功能有助于免疫抑制。最后,讨论了如何直接靶向免疫抑制细胞,以提供治疗败血症和提高长期生存率的潜在治疗效益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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