Increased Skin Inflammation and Blood Vessel Density in Human and Experimental Diabetes

Abstract

Systemic inflammation is associated with impaired wound healing in diabetic patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all diabetic animal models compared to their non-diabetic controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around pre-existing skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.

Increased number of Langerhans cells in the epidermis of diabetic foot ulcers correlates with healing outcome

“…Skin inflammation is also increased in the skin of individuals suffering from diabetes [20]. Previous studies report a difference in accumulation of LCs between normal epidermis from plantar foot skin compared to normal calf skin.…”

“…Recent studies have revealed the presence of increased skin inflammation in human diabetic skin. [20] Additionally, the correlation of an increased number of skin LCs in patients with neuropathy and diabetes compared to those with diabetes alone suggested a possible role of LCs in the generation and maintenance of neuropathic pain [21]. Although significant differences in the cellular infiltrate of acute, healing wounds versus chronic, non-healing wounds have been reported, [22–24]the correlation with a healing outcome has not been studied yet.…”

Painful neuropathy

“…It has been argued that increased local levels of pronociceptive molecules may occur in skin and could contribute to acute nociceptor activation and chronic changes to nociceptor phenotype. Inflammatory cell number has also been reported to increase in the skin of diabetic patients and animals (Tellechea et al, 2013). Inflammatory cell number has also been reported to increase in the skin of diabetic patients and animals (Tellechea et al, 2013).…”

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

“…Despite the severity of the problem, no new treatments have been licensed recently, and the only 3 commercially available products-Regranex (Becaplermin), Apligraf, and Dermagraft-are characterized by moderate efficacy. [3][4][5] Studies from our groups have identified possible mechanistic interventions that can improve DFU management; that is, we have demonstrated a persistent inflammatory state in DM that is present at baseline [6][7][8] and throughout the impaired wound healing process. 7,9 In addition, we have found reduced levels of the neuropeptide Substance P (SP) in human and experimental DM.…”