Talactoferrin stimulates wound healing with modulation of inflammation.
BACKGROUND
Inflammation is an acute, early process during normal wound healing. Talactoferrin, a recombinant human lactoferrin, can induce the secretion of inflammatory mediators.


METHODS
We measured wound healing activity of topical talactoferrin in full-thickness wounds of normal mice and diabetic (db(-)/db(-)) mice, systemic bioavailability, and the potential to modulate inflammation through in vitro and in vivo binding assays and inflammatory mediator measurements.


RESULTS
Talactoferrin significantly increased the closure rate during 12 to 19 d (maximally on d 3 to 6), the 75% closure incidence, and the time to 50% closure versus vehicle or becaplermin (recombinant human platelet-derived growth factor). Systemic bioavailability was less than 0.5% following administration to open wounds. Talactoferrin bound local dermal cells in vivo and human dermal fibroblasts in vitro, and it induced the migration of dermal fibroblasts, THP-1 macrophages, Jurkat T cells, and mouse granulocytes in vitro. Competition binding assays suggested the involvement of IL-8RB and CCR2 chemokine receptors in binding and/or cell migration. Consistently, the induction of migration was partially inhibited in interleukin (IL)-8RB deficient granulocytes. Talactoferrin also enhanced the production of key repair inflammatory mediators IL-8, IL-6, macrophage inflammatory protein-1 alpha, and tumor necrosis factor alpha in d 3 wounds, and IL-8, IL-6, and monocyte chemotactic protein-1 in cultured dermal fibroblasts.


CONCLUSIONS
Talactoferrin promotes wound repair in vivo, correlating with a modulated enhancement of the early inflammatory phase of wound healing. Based on this data, talactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective and safe. Talactoferrin should be further evaluated in patients with diabetic and other types of ulcers.
Engelmayer
Jose
J
Agennix Inc., Houston, Texas 77046, USA. jengelmayer@agennix.com
Blezinger
Paul
P
Varadhachary
Atul
A
D000279:Administration, Cutaneous; D000818:Animals; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D019169:Jurkat Cells; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017695:Soft Tissue Injuries / Q000188:drug therapy* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D018836:Inflammation Mediators; C515276:talactoferrin alfa; D007781:Lactoferrin