The molecular biology of immunologically-induced inflammation is being examined in several model systems.Recent progress: (A) We have found that immunological activation of mast cells through their IgE receptors results in the rapid transcription and secretion of high levels of interleukin (IL)-13, an IL-4-like cytokine sharing many properties with IL-4 but lacking effects upon T-cells. RNA accumulation peaked between 1 and 2 h after IgE-mediated stimulation and secreted IL-13 bioactivity reached 1-2 ng/ml of IL-13. When added to human B-lymphocytes, mast cell-derived IL-13 activity -- like bone fide IL-13 -- induced immunoglobulin Ce transcripts, DNA recombination characteristic of the isotype switch to Ce, and the secretion of IgE protein. Our studies demonstrate that mast cells stimulated through IgE are an important source of both IL-4 and IL-13, suggesting a model of local positive feedback interactions between mast cells and B cells which could play a role in the pathogenesis of atopic allergy. We also determined using a semi-quantitative PCR assay that mast cells also transcribe IL-7, IL-10, and IL-11, cytokines involved in the regulation of growth and differentiation of hematopoietic cells including B cells. We have begun an examination of the role(s) mast cell products, especially IL-13, IL-4 and endothelin-1, may play in the development of pathologic pulmonary fibrosis observed in atopic allergy and asthma, and in cyctic fibrosis.(B). We have determined that the expression of CD40 ligand by mast cells is a late maturation event and that the ligand is shed from the cell surface following activation of the cell through IgE, phorbol ester or calcium ionophore.(C). We have determined that mast cells transcribe and store perforin/cytolysin, a key mediator of cell-mediated cytotoxicity. We are currently examining the mechanisms leading to release and function of this protein.(D). We have continued our studies of the regulation of endothelin-1 expression in human monocytes and have shown that interferon-gamma regulates expression of endothelin-1 transciption and secretion.