Age-Related Alterations in the Inflammatory Response to Dermal Injury

Abstract

Previous studies have documented that the ability to heal wounds declines with age. Although many factors contribute to this age-associated deficit, one variable that has not been carefully examined is leukocyte recruitment and function in wounds. This investigation compares the inflammatory response in excisional wounds of young (age 8 wk) and aged (age 22 mo) mice. In the early inflammatory response, neutrophil content of wounds was similar for both aged and young mice. In contrast, macrophage levels were 56% higher in aged versus young mice (81 +/- 20 vs 52 +/- 13 cells per mm2). In the later inflammatory response, wounds of aged mice exhibited a delay in T cell infiltration, with maximum T cell levels at day 10 in aged mice versus day 7 in young mice. Despite this delay, the eventual peak concentration of T cells was 23% higher in the wounds of aged mice (152 +/- 11 cells per mm2 vs 124 +/- 21cells per mm2). The observed alterations in inflammatory cell content suggested that chemokine production might be altered with age. An elevation of monocyte chemoattractant protein (MCP-1) levels was observed in wounds of aged mice. RNase protection studies, however, revealed that the production of most chemokines, including MIP-2, MIP-1alpha, MIP-1beta, and eotaxin, tended to decline with age. Because optimal wound healing requires both appropriate macrophage infiltration and phagocytic activity, phagocytosis was examined. Compared to young mice, wound macrophages from aged mice exhibited a 37%-43% reduction in phagocytic capacity. Taken together, the data demonstrate age-related shifts in both macrophage and T cell infiltration into wounds, alterations in chemokine content, and a concurrent decline in wound macrophage phagocytic function. These alterations may contribute to the delayed repair response of aging.

Neutrophil depletion delays wound repair in aged mice

“…Pressure ulcers are caused by compression, friction, infection and/or malnutrition. The ability to heal pressure ulcers declines with age (Swift et al 2001). To understand the mechanism underlying the impaired ability of older patients to repair pressure ulcers, we established studies to analyze wound healing in aged mice.…”

Innate immunity in aging: impact on macrophage function

“…Using quantitative imaging, they have shown that monocyte/macrophage and lymphocyte appearance was delayed in the aged, with cell numbers peaking at Day 84, compared with Day 7 for monocytes and Day 21 for lymphocytes in the young. Furthermore, it is observed that the phagocytic ability of macrophages from aged individuals declines in parallel with the decreased levels of macrophage-derived chemokines MIP-1 α , MIP-1 β , MIP-2, and eotaxin (Swift et al ., 2001). …”

Exercise, Obesity, and Cutaneous Wound Healing: Evidence from Rodent and Human Studies

“…At the systemic level, age, gender, hormone status, obesity, stress, medication use, alcoholism, smoking, poor diet, and immunocompromisecan delay or alter healing rate. 1 Altered inflammation is associated with delayed healing in aged populations, 17 and these alterations can result in reductions in angiogenesis and remodeling of the wound site in these groups. Interestingly, although inflammation in these individuals seems to be increased, macrophage function seems to be reduced, 18 suggesting that risk of infection may be increased in aged individuals despite their abnormally high levels of local tissue inflammation.…”