Sepsis-Induced Immunosuppression

Abstract

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. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Concomitant Assessment of Monocyte HLA-DR Expression and Ex Vivo TNF-α Release as Markers of Adverse Outcome after Various Injuries—Insights from the REALISM Study

“…The present results confirm that there is an association between markers of immunosuppression and adverse outcome after various types of injury such as trauma or major surgery [8,11,28,29]. Our study also confirms the strong and independent association between each marker and adverse outcome after multivariate analysis.…”

“…However, they limited their analyses to the values measured on ICU admission, whereas our findings suggest that TNF-α values have better performance when measured at D5–D7. The lack of consistency in the association with clinical outcomes in some studies may also result from the lack of reproducibility in the measurement of TNF-α release, which has never been standardized [ 11 ]. This issue was underscored by Segre et al [ 19 ].…”

“…A better understanding of the putative role of immune alterations in clinical worsening after an injury may enable the use of agents that stimulate the immune system as a potential therapeutic strategy to reduce morbidity and mortality of critically ill patients [ 9 , 10 ]. Because the immune response during the ICU course can vary among patients and over time, it is necessary to correctly identify the patients who will most benefit from these treatments [ 11 ]. The development of reliable biomarkers to identify individuals with clinically meaningful immunosuppression is thus required [ 9 , 12 ].…”

“…However, reported results are more heterogeneous than those of mHLA-DR [ 18 , 19 , 20 ]. This may be owed to the fact that TNF-α release measurement is less standardized [ 11 , 19 ] and is based on whole blood that contains various types of leukocytes.…”

Inhibiting KDM6A Demethylase Represses Long Non-Coding RNA Hotairm1 Transcription in MDSC During Sepsis

“…Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a leading cause of death and critical illness (1,2). Sepsis may enable a profound innate and adaptive immune suppression following its acute hyperinflammatory response (3)(4)(5). The immunosuppressive state causes CD4 and CD8 T cell exhaustion (3,6), incites new infections and reactivates latent viruses (7,8), increases the incidence of chronic critical illness (9), and raises morbidity and mortality rates (3,9).…”