DIFFERENTIAL REGULATION OF PRO-INFLAMMATORY CYTOKINES DURING WOUND-HEALING IN NORMAL AND GLUCOCORTICOID-TREATED MICE

It has long been speculated that pro-inflammatory cytokines play an im portant role in wound repair, However, little is known about the tempo ral and spatial expression pattern of these cytokines during normal an d impaired wound healing, In this study we show a strong and early ind uction of interleukins 1 alpha and beta (IL-alpha and beta) and of tum our necrosis factor alpha (TNF-alpha) expression after cutaneous injur y, Highest levels of these cytokines were seen as early as 12-24 h aft er wounding, After completion of the proliferative phase of wound heal ing, mRNA levels of these cytokines returned to the basal level. Durin g the early phase of wound repair, proinflammatory cytokines were pred ominantly expressed in polymorphonuclear leukocytes, suggesting a nove l function of these cells in the initiation of wound healing, At later stages of the repair process, expression of IL-1 alpha, IL-1 beta and TNF-alpha was also seen in macrophages, Furthermore, TNF-alpha was de tected in the hyperproliferative epithelium at the wound edge and IL-1 alpha was found in keratinocytes of the hair follicles, Induction of these cytokines after injury was significantly reduced during wound re pair in healing-impaired glucocorticoid-treated mice. This finding dem onstrates that wound healing defects are associated with impaired cyto kine expression and suggests that the early induction of these genes i s important for normal repair. (C) 1996 Academic Press Limited