IL-13 has been proposed to be an autocrine
growth factor for Hodgkin/Reed-Sternberg
tumor cells (H/RS cells). Since we have recently identified and produced a novel
IL-13 antagonist (IL-13E13K) that can suppress the
biological activity of
IL-13, here we examined whether
IL-13E13K can inhibit growth of
Hodgkin lymphoma (HL)-derived cell lines.
IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous
IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed
IL-13 message and
protein and message for various chains of IL-13R. H/RS cell lines expressed
mRNA for the IL-13R alpha 1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha 2 chain. An H/RS cell line (L1236) internalized the
ligand-receptor complex after binding to a fusion
protein composed of
IL-13 and a mutated form of Pseudomonas
exotoxin A (IL-13-PE38QQR, or IL-13 cytotoxin), as
IL-13 cytotoxin was specifically cytotoxic to H/RS cells in vitro. These results indicate that
IL-13E13K and
IL-13 cytotoxin can effectively suppress growth of a L1236 H/RS cell line. Therefore, additional studies should be performed to determine the expression of
IL-13 and IL-13R in primary clinical samples of
Hodgkin's lymphoma and both agents should be further tested in vitro and in vivo as possible therapeutic agents for HL.