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.