During the past three years, a novel protein has been identified as a secretory product of endotoxin-stimulated macrophage and monocyte cultures. The protein is unique in that it induces a catabolic state in cultured murine pre-adipocytes: when differentiated mouse 3T3-L1 cells are exposed cells are exposed to exceedingly dilute concentrations of this factor, it acts to selectively inhibit their synthesis of lipoprotein lipase, acetyl CoA carboxylase, and fatty acid synthetase, thus favoring mobilization of cellular lipid stores and preventing the synthesis or uptake of fatty acids (1,2). It is felt that this protein, secreted in vivo, may be the primary mediator of cachexia in the setting of malignant disease or chronic infection. While only partially characterized, the protein is approximately 75,000 daltons in size, thermolabile, and subject to digestion by a variety of proteases. It is maximally stable between pH 6 and 8, and has a Pi of 5.6. It appears to lack any carbohydrate moiety. It comprises roughly 1 percent of the toal protein secreted by stimulated, cultured macrophages, and has been purified in active form by polyacrylamide gel electrophoresis. Further work with this protein is planned as follows: 1. Utilizing classical biochemical methodology, the protein will be purified to homogeneity in milligram quantities. 2. The purified protein will be radioiodinated. It will also be used to prepare animal antibodies in a second species of animal. 3. The iodinated material will be used to devise a receptor competition assay. 4. The antiserum will comprise the basis of a radioimmunoassay. 5. Determination of plasma factor levels will be made in various pathologic states in both animals and human subjects. These states will include cachexia of various causes, and other inbalances of triglyceride homeostatis. Additionally, we will seek to gain insight into the physiologic role of the protein as well as its function in the setting of disease, and to assess the degree to which it may contribute to the maintenance of a static triglyceride mass.
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