IDENTIFICATION OF B-CELL GROWTH-FACTORS (INTERLEUKIN-14 HIGH-MOLECULAR WEIGHT-B-CELL GROWTH-FACTORS) IN EFFUSION FLUIDS FROM PATIENTS WITH AGGRESSIVE B-CELL LYMPHOMAS

The molecular basis of neoplastic B-cell growth is complex and poorly understood, Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction , but little is known about the in vivo role of these growth factors. We have examined the production of interleukin-14 (IL-14) (high molecu lar weight [HMW], B-cell growth factor [BCGF]) by aggressive intermedi ate (diffuse large cell) lymphomas of the B-cell type non-Hodgkin's ly mphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots an d IL-14 mRNA was constitutively expressed in the freshly isolated lymp homa cells that also expressed the receptor for IL-14 (IL14R). Lymphom a B cells placed at low serum and cell density proliferated in vitro t o either purified IL-14 or IL-14 derived from effusion fluids. Antibod ies to IL-14 removed the growth-stimulating cytokine(s) from the effus ions, Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro, Thus, au tocrine:or paracrine production of IL-14 may play a significant role i n the rapid proliferation of aggressive NHL-B. Interrupting this pathw ay could be a useful goal of therapy for patients resistant to convent ional chemotherapy. (C) 1995 by The American Society of Hematology.