Impact of resolvin mediators in the immunopathology of diabetes and wound healing

ABSTRACT

Introduction: Wound healing in diabetes may be delayed by persistent wound infection due to deficient immune and cellular response to tissue injury. Hyperglycemia due to decreased insulin availability and increased insulin resistance affects the immune response of the body. Accumulation of inflammatory immune cells and pro-inflammatory cytokines results in chronic inflammation and an altered resolution and remodeling phase of wound healing.

Areas covered: Pro-resolving mediators called ‘resolvins’ target the resolution phase of wound healing and are becoming an area of increased interest. Resolvins stimulate self-limited innate immune responses and enhance innate microbial killing and clearance. Resolvins resolve inflammation by decreasing neutrophil infiltration and transmigration, increasing the phagocytic activity of macrophages, decreasing adipose tissue macrophages, downregulating platelet activation, suppressing nuclear factor-kappa beta activation, promoting the apoptosis of polymorphonuclear leukocytes, and improving insulin sensitivity. This review discusses the role of resolvins in diabetic wound healing and potential therapeutic strategies. The review is based on a literature search of PubMed and the Web of Science restricted to publications between January 2001 and October 2020.

Expert opinion: There is increasing support for the use of resolvins in clinical applications related to diabetes and wound healing. Further research will help clarify this potential.

KEYWORDS:

• Diabetic wound
• chronic inflammation
• delayed wound healing
• endogenous pro-resolving mediators
• e-resolvins
• d-resolvins

Article highlights

• Impaired resolution of inflammation leading to chronic inflammation contributes to delayed wound healing in diabetes.

• Resolvins, which are endogenous pro-resolving mediators, promote the active resolution of inflammation.

• Resolvins have a specific structure and targets.

• Neutrophils, macrophages, endothelial cells, and signaling factors are the targets of resolvins to attenuate inflammation.

• Resolvins inhibits neutrophil infiltration and transmigration, increased macrophage-mediated phagocytosis and efferocytosis, increase pro-resolving macrophages, and decrease insulin resistance.

• Resolvins enhance wound healing, angiogenesis, and re-epithelialization.

Declaration of interest

The research work of DK Agrawal is supported by research grants R01HL128063, R01 HL144125 and R01HL147662 from the National Institutes of Health, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.