Rabbit macrophages make two biochemically and immunologically distinct endogenous pyrogens (EPs). Both have been purified to apparent homogeneity. EPs are polyfunctional molecules which have the ability to promote the mitosis of T cells (Interleukin 1, IL-1 action), and to induce all the features of the acute phase response. EP/IL-1 molecules are almost certainly involved in the pathogenesis of important human diseases such as rheumatoid arthritis and pulmonary fibrosis. They have very broad species specificity; human EPs work well in rabbits or mice and lizard EP works in rabbits. No structural information is available for any EP. We now wish (1) To purify hundreds of micrograms of both forms of EP. (2) To sequence both molecules. (3) To test highly purified EPs for biological activities other than pyrogenicity. (4) To inject purified pyrogens into the rabbit hypothalamus and see whether acute phase changes are induced. (5) To study further the temperature sensitivity of IL-1 and IL-2. (6) To see if fibroblasts are temperature sensitive. (7) To radiolabel purified EPs, with a view to studying IL-1 receptors. (8) To see whether the pI 7.3 EP mRNA can be expressed in Xenopus oocytes.
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