Cytotoxic activity of a recombinant fusion protein between interleukin 4 and Pseudomonas exotoxin.

A recombinant chimeric toxin in which the cell binding domain of Pseudomonas exotoxin (PE) was replaced by murine interleukin 4 (IL-4) was produced in Escherichia coli. This chimeric protein, IL-4-PE40, was cytotoxic to murine IL-4 receptor-bearing cell lines but had little effect on human cell lines lacking receptors capable of binding murine IL-4. A mutant form of IL-4-PE40 (termed IL-4-PE40 asp553) with very low ADP-ribosylating activity displayed mitogenic activity similar to that of IL-4 rather than cytotoxic activity. Because the cytotoxic effects of IL-4-PE40 were blocked by excess IL-4 or by neutralizing antibody to IL-4 (11B11), we conclude that the cytotoxic effect of IL-4-PE40 is specifically mediated through IL-4 receptors. IL-4-PE40 could be a useful reagent for specific elimination of cells bearing IL-4 receptors.