Innate defense regulator peptide 1018 in wound healing and wound infection

PLoS One. 2012;7(8):e39373. doi: 10.1371/journal.pone.0039373. Epub 2012 Aug 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antimicrobial Cationic Peptides / therapeutic use*
  • Antimicrobial Cationic Peptides / toxicity
  • Cathelicidins / pharmacology
  • Cathelicidins / therapeutic use
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colony Count, Microbial
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / microbiology
  • Diabetes Mellitus, Experimental / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / pathology
  • Mice
  • Microbial Sensitivity Tests
  • Skin / drug effects
  • Skin / microbiology
  • Skin / pathology
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Sus scrofa
  • Treatment Outcome
  • Wound Healing / drug effects*
  • Wound Healing / immunology*
  • Wound Infection / drug therapy*
  • Wound Infection / immunology*
  • Wound Infection / microbiology
  • Wound Infection / pathology

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • innate defense regulating peptide 1018
  • CAP18 lipopolysaccharide-binding protein