Donor-specific tolerance permits burn allografting without increased sepsis

Abstract

Early excision and allografting of massive burns is beneficial. However, chronic immunosuppression, utilized to prolong allograft survival, increases the potential risk of infection. We have previously shown long-term skin allograft survival in mice with a 30% total body surface area (TBSA) burn by inducing donor-specific tolerance (DST) using only perigrafting administration of antithymocyte globulin (ATG) and donor bone marrow (DBM). Chronic immunosuppression is avoided. This study tests whether induction of DST compromises host resistance to infection. Resistance to a septic challenge created by cecal ligation and puncture (CLP) 10 days after a 30% TBSA burn was investigated in the following groups of mice: Group Mortality ∗ I. CLP, eschar intact ( n = 18) 83% II. CLP, burn excision, isograft ( n = 14) 43% III. CLP, burn excision, allograft, ATG ( n = 15) 40% IV. CLP, burn excision, allograft, ATG, DBM ( n = 14) 50% ∗ 8 days after CLP Positive blood cultures were documented for 97% of mortalities. Burn excision and grafting significantly ( P ⩽ 0.05) decreased mortality. No increased mortality was seen in allografted mice receiving ATG or ATG and DBM compared to isografted mice receiving no immunosuppression. These studies suggest that skin allografting with DST may permit the benefits of burn excision without the risks of infection seen with chronic immunosuppression.