Our work during the past three years of this study has centered around endogenous mediators of immunosuppression following major thermal injuries. Data assembled during this time period indicate the probable importance of an immunosuppressive molecular complex (containing sialic acid, a short peptide, and the metabolites of arachidonic acid; less than 5000 mw) in producing an immunologically compromised state in these burn patients. Our working hypothesis, therefore, is that this specific low molecular weight complex occurs in the plasma of a majority of patients with major thermal injuries and that it contributes to the immune depression which occurs subsequent to injury. The continued studies described in this application are focused in three areas: 1) The further characterization of the suppressor complex and its activity. This section of the proposal includes confirming the presence and the role of arachidonic acid metabolites and (possibly) albumin fragments in the suppressive complex, completion of the biochemical and physical characterization of the suppressor, and determination of the mechanism of its actibity vs. in vitro lymphocyte and neutrophil function. 2) The determination of the occurrence of the suppressor complex in the burn patient population. In these studies, we propose to develop a panel of monoclonal antibodies to the suppressor and use them to develop an ELISA-type assay for the molecular complex, and to determine the temporal occurrence of the suppressor in a broad spectrum of patients with major thermal injuries. 3) The assessment of the participation of the suppressor complex in clinically relevant immunologic changes. This final section of the proposal is concerned with using a murine animal model to characterize the activity of the suppressor, as well as with correlative statistical studies to determine cause-and-effect relationships in the patient population.
