Inhibitory Effect of Interleukin 4 on Production of Interleukin 6 by Adult T-Cell Leukemia Cells

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin 6 (IL-6), which is suggested to play an important role in thrombocytosis, elevation of C-reactive protein, and hypercalcemia in ATL. In this study, we investigated the effects of T-cell growth factors such as interleukin 2 (IL-2) and interleukin 4 (IL-4) on IL-6 production by ATL cells in vitro . Although IL-2 and/or IL-4 enhanced the cell proliferation of freshly isolated ATL cells from seven of nine patients, IL-2 did not affect the IL-6 release in most cases. In contrast, another T-cell tropic factor, IL-4 markedly inhibited the release of IL-6 in the conditioned medium in all cases. This IL-4-mediated inhibition of IL-6 release was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Time course experiments demonstrated that IL-4 reduced the secretion of IL-6 for a prolonged period of time (more than 72 h). By Northern analysis, IL-4 reduced the transcription level of IL-6 mRNA. Furthermore, by flow cytofluorometry with the use of anti-human IL-4 receptor monoclonal antibody, ATL cells showed the significant level of IL-4 receptor on their cell surfaces without any stimulation. These data suggest that IL-4 may play an important regulatory role in the production of IL-6 in ATL.