Definition of a burn injury-induced immunosuppressive serum component

We and others have previously observed that immunologic activity can often be restored to both lymphocytes and neutrophils by removing them from the burn environment, leading to the conclusion that burn serum contains substances capable of suppressing immunologic function. The present studies were initiated to better define the serum component(s) responsible for this immunosuppression. The majority of immunosuppressive activity vs. both neutrophil chemotaxis and mixed lymphocyte cultures contained in large-volume serum samples obtained from three patients with greater than 40% body surface area flame burns was found to reside in a less than 25,000 mw fraction of serum obtained by Amicon ultrafiltration. A single suppressive serum component was isolated by precipitation and resuspension, followed by ion-exchange chromatography using an SP Sephadex C-25 column. Purity of the samples was verified by SDS slab-gel electrophoresis, and immunosuppressive activity was confirmed vs. both lymphocytes and neutrophils. Analysis of this isolated burn-associated suppressor indicates: a) a molecular weight of between 1,000 and 5,000 daltons; b) a complex composition containing a protein component, a lipid component, and a carbohydrate component; c) a structure which is heat stable, pH stable and unaffected by treatment with trypsin, proteinase K, DNAse, and RNAse; and d) a noncytotoxic immunosuppressive mode of action. It appears that the suppressive activity is dependent upon a prostaglandin portion of this low molecular weight complex.