The proposed research addresses the investigation of the acute-phase response to injury, using Salmonella choleraesuis pig liver perfusions as a model. The liver was chosen as the model organ because of its major contribution of cytokines, and its exclusive contribution of acute phase proteins in the acute phase response. Based on preliminary results, the proposed research will investigate the physiologic, immunologic, pathologic and microbiologic effects of individual components of the acute phase response on the liver and on the microbes. The research will consist of 10 experiments, using 4 liver perfusions per experiment, and 4 control experiments, also involving 4 liver perfusions per control experiment. Livers will be perfused with 10(8) S. choleraesuis for 3 hours, and single and multiple components of the acute phase response will be added to the perfusion fluid at 50 minutes after S. choleraesuis introduction. The components to be investigated will comprise endotoxin, the cytokines tumor necrosis factor alpha (TNFalpha), interleukin 1 (IL-1), and interleukin 6 (IL-6), and the acute phase proteins C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin. In addition, the proposed research will investigate the combined effects of all acute phase reactants on the perfused liver. Physiologic methods used to evaluate the response of the liver.will comprise liver function tests, biochemical methods will comprise purification and quantitation of acute phase proteins, immunologic methods will comprise bioassays for cytokines TNFalpha, IL-1 and IL-6, pathologic methods will comprise histopathologic examination of perfused livers, and microbiologic methods will comprise live S choleraesuis counts from perfusion fluids and from the liver.
