ACTIVATED MAST-CELLS PRODUCE INTERLEUKIN-13

When mast cells are activated through their immunoglobulin (Ig)E recep tors, release of low molecular weight mediators like histamine is foll owed by secretion of multiple cytokines, including interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor. Her e we report that stimulated mast cells also synthesize IL-13 mRNA and protein; secretion of this cytokine may be of particular importance be cause of its ability to stimulate IgE expression. IL-13 transcripts de tected by a semiquantitative reverse transcriptase-mediated polymerase chain reaction assay were induced within 30 min after stimulation of mast cells by dinitrophenyl plus monoclonal IgE anti-dinitrophenyl, an d peaked at about 1 h. Within 3 h of IgE stimulation, secreted IL-13 b ioactivity, estimated by proliferation of an IL-13-dependent cell line , reached levels equivalent to 1-2 ng/ml of IL-13. When added to human B lymphocytes, the mast cell-derived IL-13 activity (like bone fide I L-13) induced Ig C epsilon transcripts, DNA recombination characterist ic of the isotype switch to C epsilon, and the secretion of IgE protei n. These results suggest a model of local positive feedback interactio ns between mast cells and B cells, which could play a role in the path ogenesis of atopy.