The role of interleukin 13 in classical Hodgkin lymphoma

The Reed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) produce several cytokines, which are thought to account for the unique clinical and pathologic features of this disease. We previously identified interleukin (IL)-13 expression as a common feature of cHL and have studied the potential role of this cytokine as an autocrine growth factor for RS cells. IL-13 and the IL-13-specific receptor chain (IL-13R alpha1) are frequently expressed in cHL-derived cell lines and in RS cells from biopsies of cHL tissues. In contrast, IL-13 expression in non-Hodgkin lymphoma (NHL) is uncommon. Neutralization of IL-13 in cultures of cHL-derived cell lines HDLM-2 and L-1236 leads to a dose-dependent inhibition of proliferation, and is associated with increased apoptosis in L-1236 cells. IL-13 neutralization also decreased activation of signal transducer and activator of transcription (STAT)6, an important mediator of IL-13 function. Moreover, STAT6 is often activated in RS cells from primary tumor samples, implying that IL-13 signaling is occurring in these cells in vivo. This review will describe the biologic activities of IL-13 in the immune system, and summarize the evidence implicating IL-13 as an autocrine growth factor for RS cells in cHL. Finally, we will discuss the potential influence of IL-13 on the reactive inflammatory infiltrate that is characteristic of cHL.