title: Innate defense regulator peptide 1018 in wound healing and wound infection.
abstract: Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. lars.steinstraesser@ruhr-uni-bochum.de
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
authors.forename: Tobias
authors.initials: T
authors.lastname: Hirsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Schulte
authors.forename: Maximilian
authors.initials: M
authors.lastname: Kueckelhaus
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.forename: Evgenija A
authors.initials: EA
authors.lastname: Mersch
authors.forename: Ingo
authors.initials: I
authors.lastname: Stricker
authors.forename: Nicole
authors.initials: N
authors.lastname: Afacan
authors.forename: Havard
authors.initials: H
authors.lastname: Jenssen
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D054804:Cathelicidins / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015169:Colony Count, Microbial; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D012867:Skin / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D034421:Sus scrofa; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology*; D014946:Wound Infection / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C555052:innate defense regulating peptide 1018