Indigenous intestinal bacteria cause a majority of the serious infections which complicate the course of patients with treated and untreated malignancy. Bacterial translocation is the process by which indigenous bacteria disseminate from the intestines to cause these infections. We previously demonstrated in mice that impaired immunity enhances bacterial translocation, but not to the stage of progressive systemic infection. The proposed research will determine the extent of bacterial translocation and systemic infection in specific pathogen-free mice bearing the following immunosuppressive transplantable tumors: lymphoma EL-4, leukemia L1210, sarcoma S-180, and fibrosarcoma MCA-1425. Associated immune deficiencies will be detected by concanavalin A stimulation of cultured spleen cells, quantification of delayed-type hypersensitivity to sheep erythrocytes, and by quantification of splenic hemolytic plaque-forming cells and serum hemagglutinin response after immunization with sheep ertythrocytes. The effects of cyclophosphamide, doxorubicin, and methylprednisolone on bacterial translocation and immune status will be determined in tumor-bearing and tumor-free mice. The immunostimulatory agents indomethacin, Corynebacterium parvum, and lithium also will be investigated for their abilities to prevent progression of bacterial translocation and systemic infection during tumor growth and anticancer chemotherapy. These studies will provide evidence that infections caused by intestinal bacteria which complicate treated and untreated malignancies are due to enhanced bacterial translocation, are associated with identifiable immunosuppressive predisposing factors, and are possibly preventable with immunomodulatory therapy.
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