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

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Abstract
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.