Antimicrobial peptides: Clinical relevance and therapeutic implications

Silva, Fabiano Pinheiro da; Machado, Marcel Cerqueira César

doi:10.1016/j.peptides.2012.05.014

Cited by 129 publications

(70 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And while it is known that septic patients typically have low 25OHD levels [24,25], and that vitamin D status is inversely associated with the severity of sepsis [26,27], little is known regarding the effects of vitamin D supplementation in this patient cohort. Therefore, our primary goal was to determine whether high-dose cholecalciferol (vitamin D3) supplementation in patients with severe sepsis or septic shock can: 1) rapidly influence vitamin D status; and 2) affect systemic expression of cathelicidin (LL-37), a vitamin D-dependent, endogenous, anti-microbial peptide [28]. Our secondary goal was to determine whether high-dose cholecalciferol supplementation modifies systemic cytokine levels in patients with severe sepsis or septic shock.…”

Section: Introductionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

152

160

View full text Add to dashboard Cite

Objectives To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design Randomized, placebo-controlled, trial. Setting Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients 30 adult ICU patients. Interventions Placebo (n=10) versus 200,000 IU cholecalciferol (n=10) versus 400,000 IU cholecalciferol (n=10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D (25OHD), as well as vitamin D binding protein and albumin to calculate bioavailable 25OHD. Plasma LL-37 and high sensitivity C-reactive protein (hsCRP) levels were also measured. At baseline, median (IQR) plasma 25OHD was 17 (13 to 22) ng/mL and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were: 1) total 25OHD: 3 (-3 to 8)%, 49 (30 to 82)%, and 69 (55 to 106)%, (P<0.001); 2) bioavailable 25OHD: 4 (-8 to 7)%, 45 (40 to 70)%, and 96 (58 to 136)%, (P<0.01); and 3) LL-37: -17 (-9 to -23)%, 4 (-10 to 14)%, and 30 (23 to 48)%, (P=0.04). Change in hsCRP levels did not differ between groups. A positive correlation was observed between bioavailable 25OHD and LL-37 (Spearman's rho=0.44, P=0.03), but not for total 25OHD and LL-37. Conclusions High-dose cholecalciferol supplementation rapidly and safely improves 25OHD and bioavailable 25OHD levels in patients with severe sepsis or septic shock. Changes in bioavailable 25OHD are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

152

160

View full text Add to dashboard Cite

show abstract

“…These gene-encoded 10-50 amino acid residue polyamides are either strategically deployed at barrier sites where bacterial infection can occur such as the skin and epithelial mucosa in mammals or rapidly delivered to the injury and infection sites in response of invading microorganisms [2]. The two major AMP families in humans are defensins and cathelicidins [3], both produced *E-mail: lotvos@comcast.net by neutrophils and epithelial cells and indeed share similar roles in lung and other tissue immunity [4]. In support, administration of a human neutrophil-derived defensin reduces bacterial load in the infected peritoneal cavity 24 h after infection in an experimental Klebsiella pneumoniae infection in mice [5].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

View full text Add to dashboard Cite

Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

show abstract

“…Defensins are small cysteine-rich cationic peptides made by neutrophils with cytotoxic and microbicidal properties, which act by binding to the microbial cell membrane and forming pore-like defects [135]. Defensin beta 1 (DEFB1) is implicated in the resistance of epithelial surfaces to microbial colonization and there is evidence that the DEFB1 gene may function as a tumor suppressor gene, its expression being associated with a large number of cancers [136].…”

Section: Angioinvasion Angiodestruction and Tissue Damagementioning

confidence: 99%

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

2014

J Blood Disord Transfus 2014

View full text Add to dashboard Cite

Antimicrobial peptides: Clinical relevance and therapeutic implications

Cited by 129 publications

References 89 publications

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Immunomodulatory effects of anti-microbial peptides

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

Contact Info

Product

Resources

About