Chapter 11 - Role of cytokines and chemokines in wound healing

Abstract

Wound healing of postnatal mammalian dermal tissue is a complex multistep process, which at best restores barrier function of the skin and results in scar formation in normal patients, but is defective in diabetic patients. Diabetes mellitus is a major risk factor for the development of chronic nonhealing wounds. Chronic diabetic wounds are a significant cause of morbidity and mortality, which are a major healthcare and economic burden. Chronic wounds in diabetic patients, particularly those with type 2 diabetes mellitus (T2DM), are often characterized as being more prone to chronic inflammation and delayed granulation tissue formation than similar wounds in nondiabetic patients. Although this characterization aptly describes the most prominent pathological features of diabetic wounds, the impaired wound microenvironment is burdened with high oxidative stress, upregulation of proinflammatory cytokines and downregulation of antiinflammatory cytokines, increased proteolysis, altered cellular phenotypes, aberrant growth factor production, poor neovascularization, neuropathy, and increased presence of microbial pathogens. Diabetes deleteriously affects every facet of the distinct but overlapping stages of healing, including hemostasis, inflammation, matrix deposition, angiogenesis, wound contraction, and tissue remodeling. Notably, the cytokine and chemokine milieu of the wound microenvironment orchestrates these processes. Therefore, serious attempts to understand the pathology of chronic diabetic wounds must examine the role these molecules play in diabetes. Multiple human and animal studies have made tremendous contributions toward this end. Chronic diabetic wounds show marked differences not only compared to acute nondiabetic wounds, but also between both chronic healing and nonhealing diabetic wounds. This chapter aims to describe the current knowledge of chemokine and cytokine milieu throughout the wound-healing stages to create a more cohesive narrative of chronic diabetic wounds and explores potential therapeutics to aid in healing. By the end of this chapter, one should have a richer understanding of how abnormal cytokine and chemokine activity is both a product of diabetes and contributes to pathological wound healing seen in diabetic patients, and central to the urgent clinical need for new targeted immune therapeutics.