Interleukin 13: a growth factor in hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is a malignant disorder of lymph nodes with distinctive clinical and pathologic features. These features are thought to be primarily due to the abnormal production of multiple cytokines by the malignant cell population of HL, the Reed-Sternberg (RS) cells. We have previously demonstrated that interleukin (IL)-13 expression is a common feature of HL and have studied its role as an autocrine growth factor for RS cells. IL-13 and IL-13R(alpha)1, the IL-13-specific receptor chain, are frequently expressed by HL-derived cell lines and by RS cells from biopsy material of tissues involved by HL. Neutralization of IL-13 in cultures of the HL-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. Signal transducer and activator of transcription (STAT) 6 is an important mediator of IL-13 signaling. STAT6 is constitutively activated in HL cell lines due to autocrine secretion of IL-13. STAT6 is also phosphorylated (P-STAT6) in RS cells from many primary HL samples, supporting the hypothesis that IL-13 signaling occurs in these malignant cells in vivo. Coexpression of IL-13, IL-13R(alpha)1 and P-STAT6 is uncommon in non-Hodgkin lymphomas. Following a description of the clinical and pathologic features of HL, this review will discuss the function of IL-13 as an autocrine growth factor for RS cells in HL and its potential role in mediating other features of this disease.