PMID- 30916807 OWN - NLM STAT- MEDLINE DCOM- 20190530 LR - 20190530 IS - 1600-0463 (Electronic) IS - 0903-4641 (Linking) VI - 127 IP - 6 DP - 2019 Jun TI - The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model. PG - 475-483 LID - 10.1111/apm.12946 [doi] AB - 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. CI - (c) 2019 APMIS. Published by John Wiley & Sons Ltd. FAU - Granslo, Hildegunn Norbakken AU - Granslo HN AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Department of Paediatrics, University Hospital of North Norway, Tromso, Norway. FAU - Aarag Fredheim, Elizabeth G AU - Aarag Fredheim EG AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Microbial Pharmacology and Population Ecology, Department of Pharmacy, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. FAU - Esaiassen, Eirin AU - Esaiassen E AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Department of Paediatrics, University Hospital of North Norway, Tromso, Norway. FAU - Christophersen, Lars AU - Christophersen L AD - Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. FAU - Jensen, Peter Ostrup AU - Jensen PO AD - Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. FAU - Mollnes, Tom Eirik AU - Mollnes TE AD - Research Laboratory, Nordland Hospital, Bodo, Norway. AD - Department of Immunology, Oslo University Hospital, Norway. AD - Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. FAU - Moser, Claus AU - Moser C AD - Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. FAU - Flaegstad, Trond AU - Flaegstad T AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Department of Paediatrics, University Hospital of North Norway, Tromso, Norway. FAU - Klingenberg, Claus AU - Klingenberg C AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Department of Paediatrics, University Hospital of North Norway, Tromso, Norway. FAU - Cavanagh, Jorunn Pauline AU - Cavanagh JP AD - Paediatric Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromso, Norway. AD - Department of Paediatrics, University Hospital of North Norway, Tromso, Norway. LA - eng GR - Northern Norway Regional Health Authority/ PT - Journal Article DEP - 20190426 PL - Denmark TA - APMIS JT - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica JID - 8803400 RN - 0 (Anti-Infective Agents) RN - 0 (Cytokines) RN - 0 (Oligopeptides) SB - IM MH - Animals MH - Anti-Infective Agents/*pharmacology MH - Complement Activation/drug effects MH - Cytokines/biosynthesis MH - Female MH - Hemolysis/drug effects MH - Humans MH - Immunity, Innate/drug effects MH - Inflammation/*chemically induced MH - Mice MH - Mice, Inbred BALB C MH - Oligopeptides/*pharmacology OTO - NOTNLM OT - LTX21 OT - cationic peptides OT - human whole blood model OT - murine model EDAT- 2019/03/28 06:00 MHDA- 2019/05/31 06:00 CRDT- 2019/03/28 06:00 PHST- 2018/09/06 00:00 [received] PHST- 2019/03/14 00:00 [accepted] PHST- 2019/03/28 06:00 [pubmed] PHST- 2019/05/31 06:00 [medline] PHST- 2019/03/28 06:00 [entrez] AID - 10.1111/apm.12946 [doi] PST - ppublish SO - APMIS. 2019 Jun;127(6):475-483. doi: 10.1111/apm.12946. Epub 2019 Apr 26.