Involvement of Interleukin-6 in the Autocrine Stimulation of Chronic Lymphocytic Leukemia B Cells by Tumor Necrosis Factor

Abstract

Tumor necrosis factor α (TNFα) acts as an autocrine growth factor in chronic B cell malignancies. TNF also induces production of interleukin 6 (IL-6) which stimulates B cell growth and differentiation. We have previously demonstrated increased TNFα production by (Rai) stage 0 chronic lymphocytic leukemia (B-CLL) cells and the absence of TNF production by cells from stage IV patients. In an attempt to elucidate a possible role for TNF in the malignant progression of B-CLL we investigated the possibility of IL-6 involvment in the stimulatory action of TNF on B-CLL cells. We observed that: (1) the in vitro proliferative response of B-CLL cells to recombinant human (rh)THFα was consistently inhibited by a monoclonal antibody (MoAb) against IL-6, (2) the release of IL-6 by B-CLL cells could be augmented by rhTNFα, (3) no differences were detected in the foregoing parameters between stage 0 and stage IV-derived cells and (4) despite the inhibitory action of an anti-IL-6 MoAb on the TNF-induced proliferative response of B-CLL cells, IL-6 receptor expression was undetectable in these cells. Although these findings are suggestive of an autocrine or paracrine mechanism involving TNF and IL-6, the importance of the release and action of these cytokines in the regulation of B-CLL cell growth and malignant progression still remains to be elucidated.