Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

doi:10.1038/nri3552

Cited by 2,002 publications

(2,163 citation statements)

References 169 publications

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“…Prior Ultrasound Treatment Reduces Severity of AKI in Sepsis A critical issue in sepsis is the pathologic dysregulated response to bacterial infection leading to a hyperinflammatory cytokine storm response, 18 and the lack of homeostasis from dysfunction of the neuroendocrine and immune systems leads to multiorgan dysfunction and early death. 19 Using the cecal ligation puncture (CLP) model of sepsis, 20 the rise in plasma creatinine ( Figure 10A) and circulating cytokines (Table 2) in WT mice subjected to CLP was reduced significantly by pretreatment with ultrasound.…”

Section: Ultrasound Modulates Splenocytementioning

confidence: 99%

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Gigliotti

Huang

Bajwa

et al. 2015

Journal of the American Society of Nephrology

122

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We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemiareperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and a7 nicotinic acetylcholine receptors (a7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA-induced splenic denervation also prevented ultrasoundinduced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal a7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and a7nAChR -/-mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture-induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.

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Section: Ultrasound Modulates Splenocytementioning

confidence: 99%

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Gigliotti

Huang

Bajwa

et al. 2015

Journal of the American Society of Nephrology

122

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“…Pro-and anti-inflammatory stages of the host immune response to sepsis often occur concurrently (Hotchkiss et al 2013). Researchers have sought to identify biomarkers to distinguish or predict high-risk patients.…”

Section: Introductionmentioning

confidence: 99%

Plasma Monocyte Chemoattractant Protein 1 as a Predictive Marker for Sepsis Prognosis: A Prospective Cohort Study

Zhu

Liao

Feng

et al. 2017

Tohoku J. Exp. Med.

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Sepsis is a systemic host response to infection, and patients with sepsis are frequently handled in the intensive care unit. However, mortality related to sepsis remains high throughout the world. In addition, there have been no efficient prognostic biomarkers for sepsis to be employed in clinical practice. We therefore aimed to identify prognostic biomarkers for sepsis using the chemokine/cytokine array. This study included 143 patients with sepsis, who were divided into survivor and nonsurvivor groups according to their 28-day mortality status. The cytokine array analysis was performed with plasma samples from two randomly selected patients in each sepsiofgroup. We thus identified seven cytokines with significantly and consistently different expression levels between nonsurvivors and survivors. The validity of the selected cytokines was then assessed by enzyme-linked immunosorbent assay (ELISA). We finally found monocyte chemoattractant protein 1 (MCP-1) as the most useful biomarker to distinguish the two sepsis groups; namely, non-surviving patients (n = 56) exhibited significantly higher plasma concentrations of MCP-1 compared to survivors (n = 87). MCP-1 is a CC chemokine, a potent chemoattractant that contributes to systemic inflammatory response syndrome. Areas under the receiver operating characteristic curves for prediction of 28-day mortality were 0.763 for MCP-1, 0.680 for the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, 0.64 for the Sequential Organ Failure Assessment (SOFA) score, 0.621 for procalcitonin, and 0.785 for MCP-1 plus APACHE II score. In conclusion, we propose that plasma MCP-1 is a useful biomarker in predicting outcome of sepsis.

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“…Generally, the HLA-DR level in patients with better outcomes of sepsis recovers in 1 week after administration. 6,23 Infection may be aggravated or uncontrolled in patients with immunosuppression, sometimes even causing death. 24 Meisel et al 20 and Schefold et al 25 demonstrated that awareness of the levels of mHLA-DR may help in guiding immunomodulatory therapy, shortening mechanical ventilation time and the duration of hospital stay.…”

Section: Discussionmentioning

confidence: 99%

Predicting the Outcomes of Subjects With Severe Community-Acquired Pneumonia Using Monocyte Human Leukocyte Antigen-DR

Zhuang

Wang

et al. 2015

Respir Care

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BACKGROUND:The objective was to study the level of monocyte-human leukocyte antigen-DR (mHLA-DR), an immune function-related biomarker, at 24 h after admission, to predict the outcomes of subjects with severe pneumonia. METHODS: Subjects with severe community-acquired pneumonia (n ‫؍‬ 102) were included in the study. Blood samples were collected from each subject 24 h after admission. Data regarding age, sex, P aO 2 /F IO 2 , comorbidities, occurrence of altered mental status, bacteremia, septic shock, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score within the first 24 h; the highest temperature within 24 h after admission; mechanical ventilation usage; timing of antibiotic therapy; ICU stay; and 28-d survival were collected. Expression of mHLA-DR was measured by flow cytometry. RESULTS: APACHE II score and SOFA score were significantly higher (P < .001), whereas the mHLA-DR expression was significantly lower (P < .001) in the non-survivors than in the survivors. The outcomes at day 28 after admission were significantly associated with the APACHE II score (P ‫؍‬ .002, odds ratio [OR] ‫؍‬ 1.27, 95% CI 1.10 -1.48), the SOFA score (P ‫؍‬ .003, OR ‫؍‬ 1.52, 95% CI 1.15-2.00), and mHLA-DR level (P ‫؍‬ .01, OR ‫؍‬ 0.91, 95% CI 0.85-0.98), as shown by logistic regression. The area under the receiver operating characteristic curve was 0.877 (95% CI 0.81-0.94, P < .001), 0.862 (95% CI 0.79 -0.93, P < .001), and 0.781 (95% CI 0.69 -0.87, P < .001) for APACHE II score, SOFA score, and the mHLA-DR expression, respectively. The optimal threshold for mHLA-DR level was 27.2%. Kaplan-Meier survival analysis showed that subjects with mHLA-DR > 27.2% had significantly better outcomes compared with < 27.2% level (P < .001, log rank test, hazard ratio ‫؍‬ 0.963, 95% CI 0.94 -0.99). CONCLUSIONS: mHLA-DR may be a reliable biomarker that can predict the outcomes of patients with severe community-acquired pneumonia, and 27.2% may be the cut-off value to predict the outcomes.

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Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

Cited by 2,002 publications

References 169 publications

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI

Plasma Monocyte Chemoattractant Protein 1 as a Predictive Marker for Sepsis Prognosis: A Prospective Cohort Study

Predicting the Outcomes of Subjects With Severe Community-Acquired Pneumonia Using Monocyte Human Leukocyte Antigen-DR

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