Talactoferrin stimulates wound healing with modulation of inflammation.

Abstract

BACKGROUND:

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

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Jose Engelmayer, Paul Blezinger, Atul Varadhachary
• Journal: The Journal of surgical research (J Surg Res) Vol. 149 Issue 2 Pg. 278-86 (Oct 2008) ISSN: 1095-8673 [Electronic] United States
• PMID: 18619616 (Publication Type: Journal Article)

Chemical References

• Inflammation Mediators
• talactoferrin alfa
• Lactoferrin

Topics

• Administration, Cutaneous
• Animals
• Diabetes Complications (drug therapy, metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Jurkat Cells
• Lactoferrin (administration & dosage, pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred ICR
• Soft Tissue Injuries (drug therapy, metabolism)
• Wound Healing (drug effects)