Interleukin-1 and interferony are multifunctional biological response modifiers with direct antiproliferative activity for tumor cells. This research proposal describes a three pronged attack to further understand the interaction of these effector molecules. First, modulation of cell proliferation by human recombinant interleukin-l alpha and beta in combination with recombinant interferon gammawill be examined with several target cell lines established from both malignant and non-malignant sources. Assays for inhibition or stimulation of growth will be conducted by measuring 3H-thymidine incorporation into DNA. Cytotoxicity is studied with a 3H-DNA release assay. 3H-interleukin 1beta will be used to compare receptors and to examined competitive binding. Second, the regulation of maturation in the acute monocytic leukemia line, THP-1, by interferon gamma will be studied. Cell surface markers detected by monoclonal antibodies to monocytes and granulocytes as well as morphologic, histochemical and functional changes will be monitored. Elisa assays will quantitate the production of interleukin-1beta and colony stimulating factor-1 by THP1 cells. Third, we will study the influence of interferon gamma on the following interleukin1 activities, co-mitogenesis with thymocytes, interleukin-2 synthesis, betacell activation, and sitmulation of fibroblast proliferation. The project is designed to explore the use of combinations of two well characterized modifiers in tumor therapy.
