Stress molecules in sepsis and systemic inflammatory response syndrome

Unit Cytokines and Inflammation, Institut Pasteur, 28 rue Dr. Roux, 75015 Paris, France.
FEBS Letters (Impact Factor: 3.17). 07/2007; 581(19):3723-33. DOI: 10.1016/j.febslet.2007.03.074
Source: PubMed


During sepsis, microbial derived products ("pathogen-associated molecular patterns", PAMPs) are recognized as exogenous danger signals by specific sensors of the host ("pattern recognitions receptors", PRRs). This interaction leads to the release of numerous stress proteins that are a prerequisite to fight infection, though their overzealous production can contribute to tissue damage, organ dysfunction and eventually death. In critically ill patients, translocation of PAMPs can occur from the gut, and injured tissues and cells release endogenous danger signals called "alarmins" (e.g. High mobility group box-1); that share some properties with PAMPs. Thus, numerous similarities occur during infectious and non-infectious systemic inflammation.

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Available from: Jean-Marc Cavaillon, Oct 23, 2014
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    • "The level of sCD14 is used to predict mortality and disease progression in chronic HIV patients [24], [33], in addition to other disorders, such as different cancers and hemodialysis [35], [36]. Microbial translocation results in the release of bacterial products, such as LPS and LBP, which in turn activate monocytes in various clinical situations [37], [38]. LPS and LBP levels have been shown to be increased in chronic HIV infection, but not in the acute stage. "
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    ABSTRACT: Background Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described. Methods Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18. Results In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes. Conclusions γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "Critical illness is frequently associated with a systemic inflammatory response syndrome (SIRS), characterized by physiological manifestations of inflammation (altered temperature, leukocytosis or bone marrow suppression, tachycardia and tachypnea) [1]. This inflammatory response is accompanied by biochemical and immunological evidence of immune system activation and can be precipitated by both sterile and infective insults [2]. "
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    ABSTRACT: Background Chromogranin A (CgA) as a marker of catecholamines may reflect the physiological stress load during the current critical illness which will affect the course of mechanical ventilation and the progress of the weaning process. The aim of the work was to assess the serum chromogranin level (CgA) in mechanically ventilated critically ill septic patients as a predictor of weaning and its relation to other conventional parameters. Patients and methods The present study was carried on 65 adult mechanically ventilated patients who presented with severe sepsis and septic shock in the intensive care units. The patients were included in the study after fulfilling the criteria of severe sepsis and septic shock. Patients were categorized consecutively into 2 groups: Group I: included 30 patients who were weaned successfully. Group II: included 19 patients who failed weaning. Serum chromogranin A was measured by commercially available ELISA KIT. Results The mean serum chromogranin A was significantly higher in the failed group compared to the success group on admission, after 24 h and after 72 h. The means in the failed group were 1922.21 ± 1800.86 ng/ml, 2240.16 ± 1927.84 ng/ml and 2168.26 ± 1851.16 ng/ml on admission, after 24 h and after 72 h, respectively while in the success group, they were 224.87 ± 177.9 ng/ml, 234.17 ± 165.81 ng/ml and 256.70 ± 163.81 ng/ml on admission, after 24 h and after 72 h, respectively. Conclusion The serum chromogranin A can be used as a predictor of the weaning in septic mechanically ventilated patients.
    Full-text · Article · Aug 2014
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    • "It results that the systemic inflammatory response, illustrated by cytokines, is reduced in S/C-KO mice as compared to B6J mice. It is well known that high levels of pro-inflammatory cytokines in the blood create a systemic inflammation that may lead to organ dysfunction and death [41]. Regarding the intra-peritoneal infection, the striking difference is the higher level of both local and systemic IL-10 in the susceptible mice (B6J) and the higher level of IL-1β in the peritoneal cavity of resistant mice (S/C-KO). "
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    ABSTRACT: Staphylococcus aureus is a major human opportunistic pathogen responsible for a broad spectrum of infections ranging from benign skin infection to more severe life threatening disorders (e.g. pneumonia, sepsis), particularly in intensive care patients. Scavenger receptors (SR-A and CD36) are known to be involved in S. aureus recognition by immune cells in addition to MARCO, TLR2, NOD2 and α5β1 integrin. In the present study, we further deciphered the contribution of SR-A and CD36 scavenger receptors in the control of infection of mice by S. aureus. Using double SR-A/CD36 knockout mice (S/C-KO) and S. aureus strain HG001, a clinically relevant non-mutagenized strain, we showed that the absence of these two scavenger receptors was protective in peritoneal infection. In contrast, the deletion of these two receptors was detrimental in pulmonary infection following intranasal instillation. For pulmonary infection, susceptible mice (S/C-KO) had more colony-forming units (CFU) in their broncho-alveolar lavages fluids, associated with increased recruitment of macrophages and neutrophils. For peritoneal infection, susceptible mice (wild-type) had more CFU in their blood, but recruited less macrophages and neutrophils in the peritoneal cavity than resistant mice. Exacerbated cytokine levels were often observed in the susceptible mice in the infected compartment as well as in the plasma. The exception was the enhanced compartmentalized expression of IL-1β for the resistant mice (S/C-KO) after peritoneal infection. A similar mirrored susceptibility to S. aureus infection was also observed for MARCO and TLR2. Marco and tlr2 -/- mice were more resistant to peritoneal infection but more susceptible to pulmonary infection than wild type mice. In conclusion, our results show that innate immune receptors can play distinct and opposite roles depending on the site of infection. Their presence is protective for local pulmonary infection, whereas it becomes detrimental in the peritoneal infection.
    Full-text · Article · Jan 2014 · PLoS ONE
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