Diminished production of interleukin-6 in chronic lymphocytic leukaemia (B-CLL) cells from patients at advanced stages of disease

The production of the cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in B-CLL cells from 24 patients at different stages of chronic lymphocytic B-cell leukaemia (B-CLL) was investigated in vitro . In the majority of these cases, low spontaneous IL-6 production was measured. Mitogenic stimulation with phorbol 12-myristate 13-acetate (PMA) or PMA plus interleukin-2 (IL-2) resulted in a tremendous increase in TNF-α and IL-6 production in cells representing early stage (Binet A) disease. In contrast, very little, if any, production took place in cells from patients with advanced stage (Binet C) B-CLL. The results from stage B patients were intermediate. The most remarkable difference was recorded in PMA-stimulated (1 ng/ml) IL-6 production. In stimulated 72 h cultures, IL-6 concentrations were 1280 ± 1080 pg/ml for Binet A ( n  = 11), 757 ± 597 pg/ml for Binet B ( n  = 8) and 46.0 ± 84.0 pg/ml for Binet C ( n  = 5). The differences in IL-6 production between stage C v B and stage C v A were both statistically significant ( P  = 0.025). Similar effects, but to a lesser extent, were observed in TNF-α production. These results suggest that the varying capacity to produce IL-6 and TNF-α may play a role in B-CLL progression and in clinical manifestations of the disease.