An excess in glucocorticoid steroids, either from endogenous or exogenous sources, has been shown to inhibit wound repair. Key to this impairment is a diminution of the inflammatory response to wounding, fibroplasia, capillary formation, reparative tissue collagen accumulation, and wound breaking strength. Because a single local application at operation of nonviable Staphylococcus aureus or its peptidoglycan increases all of these processes in normal rats, we hypothesized that nonviable S. aureus and S. aureus peptidoglycan would each ameliorate glucocorticoid-induced impaired healing. Sprague-Dawley male rats aseptically received two 7 cm paravertebral skin incisions and underwent subcutaneous implantation of polyvinyl alcohol sponges. Two glucocorticoids were used: hydrocortisone, 8 mg intramuscularly, daily beginning 1 day before operation and continuing during the postoperative period; or a single dose of a long-acting preparation of methylprednisolone, 6 or 8 mg intramuscularly, on the day before operation. Controls received intramuscular injections of saline solution at the same respective times. At the time of the operation, one incision and the polyvinyl alcohol sponges on one side of the animal were instilled with saline solution while the incision and sponges on the opposite side were instilled with nonviable S. aureus (hydrocortisone study) or S. aureus peptidoglycan (two methylprednisolone studies). The data showed that, at postoperative day 7, the single local application at wounding of nonviable S. aureus or S. aureus peptidoglycan increased wound breaking strength in the control rats by factors of 1.6 in the hydrocortisone experiment and 1.4 and 1.6 in the methylprednisolone studies. These treatments prevented (in hydrocortisone-treated rats) or mitigated (in methylprednisolone-treated rats) the glucocorticoid-induced decrease in wound breaking strength. In addition, these treatments prevented the glucocorticoid-induced decreases in the inflammatory (largely mononuclear cells) response to wounding and in the accumulation within the polyvinyl alcohol sponge of reparative tissue fibroblasts, capillaries, and collagen.
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