Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock

Barbeiro, Denise Frediani; Barbeiro, Hermes Vieira; Zampieri, Fernando Godinho; Machado, Marcel Cerqueira César; Filho, Francisco Torggler; Cunha, Débora Maria Gomes; Goulart, Alessandra Carvalho; Velasco, Irineu Tadeu; Neto, Luiz Monteiro da Cruz; Souza, Heraldo Possolo de; Silva, Fabiano Pinheiro da

doi:10.1016/j.micinf.2013.01.001

Cited by 37 publications

(23 citation statements)

References 32 publications

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“…found lower hCAP18 levels in critically ill patients (N = 49) compared to healthy controls (N = 21) [25]. In a larger study (N = 130), no difference in hCAP18 levels was detected among ICU patients with vs. without sepsis [49]. A third study, which was conducted among hemodialysis outpatients, reported an inverse association between hCAP18 levels and 1-year infection-related mortality [24].…”

Section: Discussionmentioning

confidence: 99%

Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients

et al. 2015

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IntroductionDecreased production of cathelicidin antimicrobial protein-18 (hCAP18) has been proposed to be a key mechanism linking decreased 25-hydroxyvitamin D (25D) levels with adverse outcomes among critically ill patients. However, few studies in humans have directly assessed plasma hCAP18 levels, and no study has evaluated the association between hCAP18 levels and adverse outcomes among critically ill patients.MethodsWe performed a single-center, prospective cohort study among 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012. We measured plasma hCAP18, 25D, D-binding protein, and parathyroid hormone levels on ICU day 1. The primary endpoint was 90-day mortality. Secondary endpoints included hospital mortality, sepsis, acute kidney injury, duration of mechanical ventilation, and hospital length of stay.ResultsICU day 1 hCAP18 levels were directly correlated with 25D levels (Spearman’s rho (rs) = 0.30, P = 0.001). In multivariate analyses adjusted for age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, patients with hCAP18 levels in the lowest compared to highest tertile on ICU day 1 had a 4.49 (1.08 to 18.67) greater odds of 90-day mortality, and also had greater odds of sepsis. ICU day 1 levels of other analytes were not associated with 90-day mortality.ConclusionsLower 25D levels on ICU day 1 are associated with lower hCAP18 levels, which are in turn associated with a greater risk of 90-day mortality. These findings provide a potential mechanistic basis for the frequently observed association between low 25D levels and poor outcomes in critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0812-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients

et al. 2015

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“…Barbeiro et al found that expression of LL‐37 in neutrophils separated from the peripheral blood of septic shock patients was comparable to a healthy control group; however, expression doubled in septic patients during the recovery phase .…”

Section: Ll‐37 and Immune Systemmentioning

confidence: 99%

Unique features of human cathelicidinLL‐37

et al. 2015

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Cathelicidins are antimicrobial peptides produced by humans and animals in response to various pathogenic microbes. This review intends to provide a brief overview of the expression, structure, properties and function of human cathelicidin LL-37 which may be a therapeutic agent against a variety of bacterial and viral diseases, cancers, and hard-to-heal wounds. Cathelicidins act as a primary defense against bacteria and other pathogens in the case of inflammation. They are able to kill bacteria and fungi, inhibit and destroy bacterial biofilms, and possess antiviral and antiparasitics properties. They can also play a role in angiogenesis, wound healing, and the regulation of apoptosis. The host defense peptide LL-37 has emerged as a novel modulator of tumor growth and metastasis in carcinogenesis of various types of cancers. LL-37 is an antimicrobial peptide able of inducing various effects. It acts as an anti- and pro- inflammatory factor. Cathelicidins are able to directly and selectively destroy membranes of various microbes and cancer cells, but they do not attack normal cells. The role of cathelicidins in cancer is double-sided. They play an important role in killing cancer cells and may provide a new possibility for the development of cancer therapeutics. However, they also can participate in carcinogenesis. Due to its activity spectrum LL-37 could be applied in pharmacotherapy. Cathelicidin peptides could serve as a template for the development of modern anti-microbial and anti-viral drugs. LL-37 is an excellent candidate to develop into therapeutics for infected wounds.

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“…In clinical studies, some conflicting results on circulating LL‐37 levels in septic patients have yielded. These studies respectively reported that serum LL‐37 levels are increased, decreased or unchanged in patients with sepsis . Moreover, the correlation between serum LL‐37 levels and cardiac dysfunction in septic patients has not been investigated yet.…”

Section: Discussionmentioning

confidence: 99%

Cathelicidin deficiency exacerbates cardiac dysfunction in lipopolysaccharide‐induced endotoxaemic mice

Zhai

Zhang

et al. 2020

Clin Exp Pharma Physio

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The therapeutic potential of the antimicrobial peptide cathelicidin (Camp) administration in sepsis has been widely investigated. However, little is known about the pathophysiological roles of cathelicidin in septic cardiomyopathy. In a lipopolysaccharide (LPS)‐induced endotoxaemic model, we found that the mRNA and protein expression of cardiac cathelicidin were induced in C57BL/6J wild‐type (WT) mice upon LPS challenge, accompanied by increased circulating cathelicidin levels. We showed that this peptide was mainly derived from neutrophils and monocytes/macrophages. Camp deficiency exacerbated LPS‐induced myocardial depression, while the administration of CRAMP (the mature form of mouse cathelicidin) decreased the LPS‐induced mortality in a D‐galactosamine hydrochloride (D‐GalN)‐sensitized endotoxin shock model. In vivo, LPS‐treated Camp knockout mice had a significant higher protein level of myocardial and circulating tumour necrosis factor‐alpha (TNF‐α), a major contributing factor to septic cardiomyopathy, compared to LPS‐treated WT mice, while CRAMP administration inhibited LPS‐induced TNF‐α production in the heart and plasma in D‐GalN‐sensitized endotoxaemic mice. In vitro, CRAMP treatment suppressed LPS‐induced Tnf‐α mRNA expression in cultured neonatal mouse cardiomyocytes and reduced TNF‐α secretion in the culture supernatant. The inhibitory effects of CRAMP on TNF‐α production may be related to its neutralizing ability of LPS, since CRAMP application had no effects on another toll‐like receptor 4 ligand paclitaxel‐induced Tnf‐α mRNA expression in cardiomyocytes. These findings suggest that LPS‐induced cathelicidin protects the heart against myocardial depression partly through the inhibition of TNF‐α production via neutralizing LPS.

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Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock

Cited by 37 publications

References 32 publications

Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients

Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients

Unique features of human cathelicidinLL‐37

Cathelicidin deficiency exacerbates cardiac dysfunction in lipopolysaccharide‐induced endotoxaemic mice

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