SYSTEMIC ADMINISTRATION OF INTERFERON-GAMMA IMPAIRS WOUND-HEALING

Interferon-gamma (IFN-gamma), a cytokine that has been shown to upregu late macrophage function, has recently been demonstrated to improve ou tcome when exogenously administered in several animal models of injury . Because the macrophage is also important in the events that govern w ound healing, we evaluated the effects of IFN-gamma upon wound healing in a murine model. IFN-gamma was administered in doses of 937.5-22,50 0 u synchronous with the creation of a left paraspinous wound and then daily. At Day 10, wounds were harvested, evaluated for wound disrupti on strength (WDS), and subjected to morphometric analysis. Wounds were also subjected to 36-hr formalin fixation to maximally cross-link col lagen fibrils and retested for WDS. We found that IFN-gamma impaired w ound healing at all doses relative to control, and WDS was impaired in a dose-dependent fashion. Our highest dose of IFN-gamma (22,500 u) pr oduced a WDS only 65% of the control. Morphometric studies demonstrate d less collagen deposition and a lower degree of neovascularity in IFN -gamma-treated animals. In addition, formalin fixation studies suggest ed that IFN-gamma may impair collagen cross-linking. The potential ben efits of IFN-gamma in the multiply injured patient must be weighed aga inst the possibility that IFN-gamma might deleteriously effect events fundamental to wound healing. (C) 1994 Academic Press, Inc.