Sepsis-Induced Immunosuppression

被引:190
作者
Torres, Lisa K. [1 ]
Pickkers, Peter [2 ]
van der Poll, Tom [3 ]
机构
[1] Weill Cornell Med, New York Presbyterian Hosp, Dept Med, Div Pulm & Crit Care Med, New York, NY 10021 USA
[2] Radboud Univ Nijmegen, Dept Intens Care Med, Med Ctr, Nijmegen, Netherlands
[3] Univ Amsterdam, Amsterdam Univ Med Ctr, Ctr Expt & Mol Med, Div Infect Dis, Amsterdam, Netherlands
基金
欧盟地平线“2020”;
关键词
TUMOR-NECROSIS-FACTOR; STIMULATING FACTOR THERAPY; PROGRAMMED CELL-DEATH; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; IMPROVES SURVIVAL; T-CELLS; GM-CSF; EPIGENETIC REGULATION; SECONDARY INFECTIONS;
D O I
10.1146/annurev-physiol-061121-040214
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy.
引用
收藏
页码:157 / 181
页数:25
相关论文
共 142 条
[11]   IFN-γ: A cytokine at the right time, is in the right place [J].
Burke, J. Daniel ;
Young, Howard A. .
SEMINARS IN IMMUNOLOGY, 2019, 43
[12]   Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia [J].
Burnham, Katie L. ;
Davenport, Emma E. ;
Radhakrishnan, Jayachandran ;
Humburg, Peter ;
Gordon, Anthony C. ;
Hutton, Paula ;
Svoren-Jabalera, Eduardo ;
Garrard, Christopher ;
Hill, Adrian V. S. ;
Hinds, Charles J. ;
Knight, Julian C. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2017, 196 (03) :328-339
[13]   Impact of sepsis on CD4 T cell immunity [J].
Cabrera-Perez, Javier ;
Condotta, Stephanie A. ;
Badovinac, Vladimir P. ;
Griffith, Thomas S. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2014, 96 (05) :767-777
[14]   Epigenetic regulation of immune cell functions during post-septic immunosuppression [J].
Carson, William F. ;
Cavassani, Karen A. ;
Dou, Yali ;
Kunkel, Steven L. .
EPIGENETICS, 2011, 6 (03) :273-283
[15]   Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis [J].
Carson, William F., IV ;
Cavassani, Karen A. ;
Ito, Toshihiro ;
Schaller, Matthew ;
Ishii, Makoto ;
Dou, Yali ;
Kunkel, Steven L. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2010, 40 (04) :998-1010
[16]   Bench-to-bedside review: Endotoxin tolerance as a model of leukocyte reprogramming in sepsis [J].
Cavaillon, Jean-Marc ;
Adib-Conquy, Minou .
CRITICAL CARE, 2006, 10 (05)
[17]   The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth [J].
Cavassani, Karen A. ;
Carson, William F. ;
Moreira, Ana Paula ;
Wen, Haitao ;
Schaller, Matthew A. ;
Ishii, Makoto ;
Lindell, Dennis M. ;
Dou, Yali ;
Lukacs, Nicholas W. ;
Keshamouni, Venkateshwar G. ;
Hogaboam, Cory M. ;
Kunkel, Steven L. .
BLOOD, 2010, 115 (22) :4403-4411
[18]   Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis [J].
Chang, Katherine ;
Svabek, Catherine ;
Vazquez-Guillamet, Cristina ;
Sato, Bryan ;
Rasche, David ;
Wilson, Strother ;
Robbins, Paul ;
Ulbrandt, Nancy ;
Suzich, JoAnn ;
Green, Jonathan ;
Patera, Andriani C. ;
Blair, Wade ;
Krishnan, Subramaniam ;
Hotchkiss, Richard .
CRITICAL CARE, 2014, 18 (01)
[19]   Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future [J].
Chen, Lieping ;
Han, Xue .
JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (09) :3384-3391
[20]   Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis [J].
Cheng, Shih-Chin ;
Scicluna, Brendon P. ;
Arts, Rob J. W. ;
Gresnigt, Mark S. ;
Lachmandas, Ekta ;
Giamarellos-Bourboulis, Evangelos J. ;
Kox, Matthijs ;
Manjeri, Ganesh R. ;
Wagenaars, Jori A. L. ;
Cremer, Olaf L. ;
Leentjens, Jenneke ;
van der Meer, Anne J. ;
van de Veerdonk, Frank L. ;
Bonten, Marc J. ;
Schultz, Marcus J. ;
Willems, Peter H. G. M. ;
Pickkers, Peter ;
Joosten, Leo A. B. ;
van der Poll, Tom ;
Netea, Mihai G. .
NATURE IMMUNOLOGY, 2016, 17 (04) :406-+