The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model

Hildegunn Norbakken Granslo, Elizabeth G Aarag Fredheim, Eirin Esaiassen, Lars Christophersen, Peter Østrup Jensen, Tom Eirik Mollnes, Claus Moser, Trond Flaegstad, Claus Klingenberg, Jorunn Pauline Cavanagh

Abstract

The global spread of antimicrobial resistance and the increasing number of immune-compromised patients are major challenges in modern medicine. Targeting bacterial virulence or the human host immune system to increase host defence are important strategies in the search for novel antimicrobial drugs. We investigated the inflammatory response of the synthetic short antimicrobial peptide LTX21 in two model systems: a human whole blood ex vivo model and a murine in vivo peritoneum model - both reflecting early innate immune response. In the whole blood model, LTX21 increased the secretion of a range of different cytokines, decreased the level of tumour necrosis factor (TNF) and activated the complement system. In a haemolysis assay, we found 2.5% haemolysis at a LTX21 concentration of 500 mg/L. In the murine model, increased influx of white blood cells (WBCs) and polymorphonuclear neutrophils (PMNs) in the murine peritoneal cavity was observed after treatment with LTX21. In addition, LTX21 increased monocyte chemoattractant protein-1 (MCP-1). In conclusion, LTX21 affected the inflammatory response; the increase in cytokine secretion, complement activation and WBC influx indicates an activated inflammatory response. The present results indicate the impact of LTX21 on the host-pathogen interplay. Whether this will also affect the course of infection has to be investigated.

OriginalsprogEngelsk
TidsskriftAPMIS - Journal of Pathology, Microbiology and Immunology
Vol/bind127
Udgave nummer6
Sider (fra-til)475-483
Antal sider9
ISSN0903-4641
DOI
StatusUdgivet - jun. 2019

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