Age-related alterations in the inflammatory response to dermal injury

Previous studies have documented that the ability to heal wounds declines w ith age. Although many factors contribute to this age-associated deficit, o ne variable that has not been carefully examined is leukocyte recruitment a nd function in wounds. This investigation compares the inflammatory respons e in excisional wounds of young (age 8 wk) and aged (age 22 mo) mice. In th e early inflammatory response, neutrophil content of wounds was similar for both aged and young mice. In contrast, macrophage levels were 56% higher i n aged versus young mice (81 +/- 20 vs 52 +/- 13 cells per mm(2)). In the l ater 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 2 the wounds of aged mice (152 +/- 11 cells per mm vs 124 +/- 21 cells per mm 2). The observed alterations in inflammatory cel l 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 th e production of most chemokines, including MIP-2, MIP-1 alpha, MIP-1 beta, and eotaxin, tended to decline with age. Because optimal wound healing requ ires both appropriate macrophage infiltration and phagocytic activity, phag ocytosis 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 infil tration into wounds, alterations in chemokine content, and a concurrent dec line in wound macrophage phagocytic function. These alterations may contrib ute to the delayed repair response of aging.