Lymphocyte Immunosuppression and Dysfunction Contributing to Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS)

Bergmann, Christian B; Beckmann, Nadine; Salyer, Christen E; Crisologo, Peter A.; Nomellini, Vanessa; Caldwell, Charles C.

doi:10.1097/shk.0000000000001675

Cited by 20 publications

(21 citation statements)

References 210 publications

(357 reference statements)

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“…An imbalance between proinflammatory processes and immunosuppression is thought to contribute to sepsis, which is a fatal disease [17]. Some sepsis survivors who suffer from immune disorders can progress to PICS, leading to prolonged recovery after the acute phase inflammatory insult [7]. This state of sepsis is considered to occur through varieties of internal and external factors, including a lack of adaptive immune cell reactivity, dysfunction, or loss of T cells and B cells [7,16].…”

Section: Discussionmentioning

confidence: 99%

“…Some sepsis survivors who suffer from immune disorders can progress to PICS, leading to prolonged recovery after the acute phase inflammatory insult [7]. This state of sepsis is considered to occur through varieties of internal and external factors, including a lack of adaptive immune cell reactivity, dysfunction, or loss of T cells and B cells [7,16]. Lymphocyte immunosuppression and dysfunction are key factors that contribute to the development of chronic immune disbalance and PICS [7].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, sepsis is able to impair their proliferative and effector functions to antigen-mediated stimuli [5]. Persistent immune imbalance leads some sepsis survivors to present with persistent inflammation, immunosuppression, and catabolic syndrome (PICS), characterized by a significant decrease in T lymphocytes [6,7]. The design that targeted immunoregulatory therapy based on T cells is considered to be a potential measurement to improve the prognosis of sepsis.…”

Section: Introductionmentioning

confidence: 99%

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DDX3X mRNA Expression in T Cells Is Associated with the Severity and Mortality of Septic Patients

et al. 2022

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Purpose. DDX3X acts as the critical checkpoint of death in stressed cells. The purpose of this study was to evaluate the mRNA expression level of DDX3X in T cells in peripheral blood of patients with sepsis and to explore its correlation with the prognosis of sepsis. Methods. Seventy-nine patients with traumatic sepsis were enrolled in this prospective cohort study. Blood samples were collected within 24 hours after the diagnosis of sepsis or septic shock, and the mRNA expression level of DDX3X in T cells was detected by PCR. Results. The level of DDX3X mRNA in T cells was significantly increased in septic patients as well as in septic shock patients. The level of DDX3X mRNA was negatively correlated with T cell count and positively correlated with acute physiological and chronic health assessment (APACHE) score and sequential organ failure assessment (SOFA) score ( P < 0.01 ). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.79 (95% confidence interval (CI), 0.68-0.90). A Cox proportional hazard model identified an association between an increased DDX3X mRNA level (≥1.575) and the risk of 28-day mortality ( hazard ratio = 9.540 , 95% CI, 2.452-37.108). Conclusions. High level of DDX3X mRNA in T cells in sepsis is associated with the severity of sepsis and the mortality of patients with sepsis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DDX3X mRNA Expression in T Cells Is Associated with the Severity and Mortality of Septic Patients

et al. 2022

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“…The reason contributing to an immunosuppressive state is marked by T cell exhaustion and increased proportions of regulatory T cells (Tregs), lymphopenia, etc. [ 7 ]. Lymphopenia is considered a typical sign of immunosuppression in clinical practice [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model

Liu

Wang

Feng

et al. 2021

Journal of Immunology Research

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Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which usually results in extended recovery periods and multiple complications. Alpinetin is a flavonoid isolated from Alpinia katsumadai Hayata that has been demonstrated to have anti-inflammatory, antibacterial, and antioxidant activities. The aim of this study was to investigate whether the administration of alpinetin could attenuate PICS in a septic mouse model. Mice were randomly divided into four groups: the (1) sham-operated group, (2) sham+alpinetin (1 mg/kg intravenously infused for once per day after sham operation), (3) cecal ligation and puncture (CLP), and (4) CLP+alpinetin (50 mg/kg intravenously infused for once per day after CLP). Eight days after sham operation or CLP surgery, mice were euthanized for subsequent examination. Alpinetin significantly improved the survival of septic mice. Also, it attenuated the CLP-induced persistent inflammation, immunosuppression, and catabolism syndrome. The level of plasma proinflammatory cytokines and apoptosis of T lymphocytes were obviously decreased by alpinetin as well. Moreover, oxidative stress in the organs was compelling lower in the alpinetin-treated CLP mice. In this clinically relevant model of sepsis, alpinetin ameliorates CLP-induced organ dysfunction and improves the likelihood of survival, possibly through suppressing the inflammatory response, oxidative stress, and apoptosis. These findings suggested that alpinetin could be a potential novel therapeutic approach to prevent sepsis-induced PICS.

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“…Although few biomarkers, mainly represented by cytokine signaling (the so-called cytokine storm), have been useful to predict outcome during severe COVID-19 pneumonia, in the postacute phase the utility of these biomarkers is less clear. A complex interplay of persistent inflammation, immunosuppression, and high catabolism may identify a set of immune-metabolic biomarkers associated with PACS [ 12 ].…”

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confidence: 99%

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome

Milić

Barbieri

Gozzi

et al. 2022

Open Forum Infectious Diseases

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Background Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (p<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

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Lymphocyte Immunosuppression and Dysfunction Contributing to Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS)

Cited by 20 publications

References 210 publications

DDX3X mRNA Expression in T Cells Is Associated with the Severity and Mortality of Septic Patients

DDX3X mRNA Expression in T Cells Is Associated with the Severity and Mortality of Septic Patients

Alpinetin Attenuates Persistent Inflammation, Immune Suppression, and Catabolism Syndrome in a Septic Mouse Model

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome

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