THE RELATIONSHIP BETWEEN INTERFERON-GAMMA AND KERATINOCYTE ALLOANTIGEN EXPRESSION AFTER BURN INJURY

Background Cultured keratinocyte (CK) and cadaveric skin allografts ha ve prolonged survival in patients with massive thermal injury. It is u nclear ii this delayed rejection is due to impaired host responsivenes s or decreased graft immunogenicity. Although burn injury has been sho wn to decrease parameters of allograft response, no studies have exami ned the effect of burn injury on alloantigen expression. This study in vestigated the effect of burn size on class II antigen expression in C K allografts as well as on tissue levels of interferon-gamma (IFN-gamm a), the principle regulator of alloantigen expression. Methods Anesthe tized CBA mice (n = 64) received a 0%, 20% partial-thickness (PT), 20% full-thickness (FT), or 40% FT contact burn. Forty-eight hours later, wounds were partially excised and covered with CK allografts from C57 BL/6 donors. Five days after burn injury, grafts were analyzed for don or-specific class II antigen. Protein expression was determined by Wes tern immunoblotting and quantified with video densitometry. Wound, ser um, and unburned skin levels of IFN-gamma were determined by enzyme-li nked immunosorbent assay. Groups were compared by Fisher's analysis of variance. Results As burn size increased, class II antigen expression decreased (p < 0.001). This corresponded with decreased wound and ski n levels of IFN-gamma after 40% burn (p < 0.05); however, wound IFN-ga mma was significantly elevated after 20% PT and FT burns (p < 0.01). S erum IFN-gamma increased as burn size increased (p < 0.01). Conclusion s Burn injury decreases the antigenicity of CK allografts, which partl y explains delayed allograft rejection after burn injury. Although wou nd IFN-gamma increases after minor thermal injury, the profound decrea se in wound and skin IFN-gamma after a major burn corresponds with dim inished class II antigen expression. The decreased availability of IFN -gamma after major thermal injury provides a mechanism for limited all ograft tolerance.