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      Interleukin-26 is a promising biomarker of sepsis but is it always reliable?

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          Abstract

          We read with interest the recent article by Tu et al. concluding that interleukin-26 (IL-26) is a better predictor of 28-day mortality in septic patients when compared with C-reactive protein (CRP) and procalcitonin (PCT) [1]. However, SOFA score remains the best predictor by far over IL-26. While we applaud the results of this study, we would like to make some comments. IL-26 is the most recently identified member of the IL-20 cytokine subfamily and is a promising mediator of inflammation overexpressed in activated or transformed T cells [2]. IL-26 has a molecular weight ranging between 19 and 36 kDa. Nearly half of critically ill patients especially those with septic shock have or develop acute kidney injury (AKI), and 20–25% will need renal replacement therapy (RRT) within the first week of their stay [3]. Out of the 52 septic patients in this study, several patients will develop AKI and necessitate continuous RRT (CRRT) [1]. The serum for IL-26 was taken on admission in the intensive care unit (ICU) in this study, and nothing can be said about the reliability of the admission level. Nevertheless, we would like to warn the clinician about daily monitoring of IL-26 like for CRP and PCT. CRRT is performed using membranes that have a cutoff value of 35–40 kDa, and therefore, some quantity of IL-26 will be eliminated by CRRT [4]. New highly adsorptive membranes (HAM) that can adsorb many molecules with a molecular weight above 35 kDa will even increase this removal [5]. This can mislead patient prognostication by artificially decreasing IL-26, but no studies have challenged this issue yet. Such studies should be done as there is already a long list of biomarkers in sepsis that are lacking reliability during CRRT [5]. To date, no single sepsis biomarker can be reliable during CRRT. While admission levels of IL-26 might be a good marker of severity and mortality of sepsis, this might not be the case for septic shock under CRRT [4, 5].

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          IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

          Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin.
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            An update on membranes and cartridges for extracorporeal blood purification in sepsis and septic shock

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              Interleukin-26 is overexpressed in human sepsis and contributes to inflammation, organ injury, and mortality in murine sepsis

              Background Sepsis is a serious syndrome that is caused by an unbalanced host inflammatory response to an infection. The cytokine network plays a pivotal role in the orchestration of inflammatory response during sepsis. IL-26 is an emerging proinflammatory member of the IL-10 cytokine family with multifaceted actions in inflammatory disorders. However, its role in the pathogenesis of sepsis remains unknown. Methods Serum IL-26 level was measured and analyzed in 52 septic patients sampled on the day of intensive care unit (ICU) admission, 18 non-septic ICU patient controls, and 30 healthy volunteers. In addition, the effects of recombinant human IL-26 on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis were determined. Results On the day of ICU admission, the patients with sepsis showed a significant increase in serum IL-26 levels compared with ICU patient controls and healthy volunteers, and the serum IL-26 levels were related to the severity of sepsis. Nonsurvivors of septic patients displayed significantly higher serum IL-26 levels compared with survivors. A high serum IL-26 level on ICU admission was associated with 28-day mortality, and IL-26 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, administration of recombinant human IL-26 increased lethality in CLP-induced polymicrobial sepsis. Despite a lower bacterial load, septic mice treated with recombinant IL-26 had higher concentrations of IL-1β, IL-4, IL-6, IL-10, IL-17A, TNF-α, CXCL1, and CCL2 in peritoneal lavage fluid and blood and demonstrated more severe multiple organ injury (including lung, liver and kidney) as indicated by clinical chemistry and histopathology. Furthermore, septic mice treated with recombinant human IL-26 showed an increased neutrophil recruitment to the peritoneal cavity. Conclusions Septic patients had elevated serum IL-26 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-26 in increasing lethality despite promoting antibacterial host responses. Electronic supplementary material The online version of this article (10.1186/s13054-019-2574-7) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Patrick.Honore@CHU-Brugmann.be
                Aude.Mugisha@CHU-Brugmann.be
                Leonel.BarretoGutierrez@CHU-brugmann.be
                Sebastien.Redant@CHU-Brugmann.be
                Keitiane.Kaefer@CHU-Brugmann.be
                Andrea.Gallerani@CHU-Brugmann.be
                David.DeBels@CHU-Brugmann.be
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                6 December 2019
                6 December 2019
                2019
                : 23
                : 397
                Affiliations
                ISNI 0000 0004 0469 8354, GRID grid.411371.1, ICU Department, , Centre Hospitalier Universitaire Brugmann, ; Place Van Gehuchtenplein, 4, 1020 Brussels, Belgium
                Article
                2691
                10.1186/s13054-019-2691-3
                6896507
                31810467
                c4ae7e8e-b487-4523-9015-ab4c02aec0b6
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 September 2019
                : 29 November 2019
                Categories
                Letter
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                © The Author(s) 2019

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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