Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing

Abstract

Age-related changes in the human inflammatory response in vivo have been largely ignored, resulting in a lack of understanding of the patho-physiologic processes involving inflammation that become increasingly important with age, of which wound repair is an important example. We have tested the hypothesis that the delay in wound healing resulting from old age is associated with an altered inflammatory response and endothelial cell adhesion molecule (CAM) profile, because CAMs influence the temporal and lineage profiles of extravasated leukocytes within a wound. Cutaneous punch biopsies were taken from 138 healthy subjects, aged 19 to 96 years; the wounds were rebiopsied at fixed time-points from Day 1 up to 3 months postwounding. Quantitative image analysis showed that there was a marked early increase in the neutrophil response in the aged with a less pronounced peak in the wounds of young subjects. Monocyte/macrophage and lymphocyte appearance was delayed in the aged with cell numbers peaking at Day 84, compared to Day 7 for monocytes and Day 21 for lymphocytes in the young, but with increased numbers of mature macrophages in the aged. E-selectin was strongly expressed in a perivascular distribution in the early wounds of the aged; however, only faint staining was seen from Day 3 to 7 in the wounds of the young. Intracellular CAM-1 and vascular CAM-1 expression exhibited an age-related delay in appearance and a reduction in staining intensity. This altered CAM profile may affect the early inflammatory wound healing response in aged humans and suggests a target for future therapeutic manipulations.