AGING ALTERS THE INFLAMMATORY AND ENDOTHELIAL-CELL ADHESION MOLECULE PROFILES DURING HUMAN CUTANEOUS WOUND-HEALING

Age-related changes in the human inflammatory response in vivo have be en 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 f rom old age is associated with an altered inflammatory response and en dothelial 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 sh owed that there was a marked early increase in the neutrophil response in the aged with a less pronounced peak in the wounds of young subjec ts. Monocyte/macrophage and lymphocyte appearance was delayed in the a ged with cell numbers peaking at Day 84, compared to Day 7 for monocyt es 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; howeve r, only faint staining was seen from Day 3 to 7 in the wounds of the y oung. Intracellular CAM-1 and vascular CAM-1 expression exhibited an a ge-related delay in appearance and a reduction in staining intensity. This altered CAM profile may affect the early inflammatory wound heali ng response in aged humans and suggests a target for future therapeuti c manipulations.