IMPAIRED WOUND-HEALING IN CUSHINGS-SYNDROME - THE ROLE OF HEAT-SHOCK PROTEINS

Background. Glucocorticoids impair wound healing and cause surgical mo rbidity. Heat shock proteins are essential to cellular stress toleranc e and are associated with glucocorticoids. The adrenal heat shock prot ein response is under hypothalmic-pituitary-adrenal-axis control, wher eas the vascular response is associated with alpha-1 receptors. Becaus e heat shock proteins affect cellular stress responses and are under h ypothalmic-pituitary-adrenal-axis control in other tissues, we postula ted an association between heat shock proteins and glucocorticoids in healing wounds. Methods. Modified Hunt-Schilling wound chambers were i mplanted subcutaneously in rats. They received subcutaneous time-relea se dexamethasone (25 mg) or placebo pellets. Wound chamber analysis an d immunocytochemistry. Results. Dexamethasone caused Cushing's syndrom e with similar to 70% weekly weight-loss and adrenal atrophy. Total wo und tissue decreased 90% with profound differences in molecular wound responses manifested by decreased heat shock protein 25, 72, and 73 in animals treated with dexamethasone despite equal protein loads. Furth ermore dexamethasone caused heat shock protein 72 redistribution by im munocytochemistry. Conclusions. This study represents the first descri ption of heat shock proteins in a wound healing model and demonstrates tissue-specific decrease of heat shock proteins with glucocorticoid t herapy. Thus the heat shock protein response is intimately associated with normal wound healing and is profoundly altered in subjects with C ushing's syndrome. Manipulation of this response may have clinical imp ortance in wound healing.