Interleukin 13 is secreted by and stimulates the growth of Hodgkin and Reed-Sternberg cells

Gene expression patterns can provide vital clues to the pathogenesis of neo plastic diseases. We investigated the expression of 950 genes in Hodgkin's disease (HD) by analyzing differential mRNA expression using microarrays. I n two independent microarray experiments, the HD-derived cell lines L428 an d KMH2 were compared with an Epstein-Barr virus (EBV)-immortalized lymphobl astoid B cell line, LCL-GK. Interleukin (IL)-13 and IL-5 were found to be h ighly expressed in the HD-derived cell lines. Examination of IL-13 and IL-5 expression by Northern blot analysis and enzyme-linked immunosorbent assay confirmed these results and revealed the expression of IL-13 in a third HD -derived cell line, HDLM2. Control LCL and EBV-negative non-Hodgkin lymphom a-derived cell lines did not express IL-13. In situ hybridization of lymph node tissue from HD patients showed that elevated levels of IL-13 were spec ifically expressed by Hodgkin/Reed-Stemberg (H/RS) tumor cells. Treatment o f a HD derived cell line with a neutralizing antibody to IL-13 resulted in a dose-dependent inhibition of H/RS cell proliferation. These data suggest that H/RS cells produce IL-13 and that IL-13 plays an important role in the stimulation of H/RS cell growth, possibly by an autocrine mechanism. Modul ation of the IL-13 signaling pathway may be a local objective for future th era peutic strategies.