title: Anti-inflammatory Properties of Antimicrobial Peptides and Peptidomimetics: LPS and LTA Neutralization.
abstract: Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) neutralization constitute potential non-antibiotic treatment strategies for sepsis - a systemic infection-induced inflammatory response. Studies on LPS- and LTA-neutralizing compounds are abundant in literature, and a number of peptides and peptidomimetics appear to display promising activity. However, in this ongoing search for potential antisepsis drug leads, it will be preferable that the assays used by different research groups lead to readily comparable data for the most efficient compounds. Here, we propose and describe standardized methods to be used for testing of novel compounds for their LPS- and LTA-neutralizing capacity with a focus on functional suppression of pro-inflammatory responses in cell-based systems. To best mimic the human in vivo conditions, we suggest the use of freshly isolated human leukocytes combined with an appropriate method for the chosen cytokine (e.g., IL-6 or TNF-α). The described protocols comprise isolation, stimulation, and viability test of the human leukocytes.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken2, Copenhagen, DK-2100, Denmark.
authors.forename: Sarah Line
authors.initials: SL
authors.lastname: Skovbakke
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken2, Copenhagen, DK-2100, Denmark. henrik.franzyk@sund.ku.dk.
authors.forename: Henrik
authors.initials: H
authors.lastname: Franzyk
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D057786:Peptidomimetics / Q000494:pharmacology*; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D057786:Peptidomimetics; D013682:Teichoic Acids; C009900:lipoteichoic acid
keywords: Cytokines; LPS neutralization; LTA neutralization; Peptides; Peptidomimetics