DIMINISHED PRODUCTION OF INTERLEUKIN-6 IN CHRONIC LYMPHOCYTIC-LEUKEMIA (B-CLL) CELLS FROM PATIENTS AT ADVANCED STAGES OF DISEASE

The production of the cytokines interleukin-6 (IL-6) and tumour necros is factor-alpha (TNF-alpha) in B-CLL cells from 24 patients at differe nt stages of chronic lymphocytic B-cell leukaemia (B-CLL) was investig ated in vitro. In the majority of these cases, low spontaneous IL-6 pr oduction was measured, Mitogenic stimulation with phorbol 12-myristate 13-acetate (PMA) or PMA plus interleukin-2 (IL-2) resulted in a treme ndous increase in TNF-alpha and IL-6 production in cells representing early stage (Binet A) disease. In contrast. very little, if any, produ ction took place in cells from patients with advanced stage (Binet C) B-CLL. The results from stage B patients were intermediate, The most r emarkable difference was recorded in PMA-stimulated (1 ng/ml) IL-6 pro duction. In stimulated 72h 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 +/- 84.0pg/ml for Binet C (n = 5), The differences in IL-6 pr oduction between stage C v B and stage C v A were both statistically s ignificant (P = 0.025). Similar effects, but to a lesser extent, were observed in TNF-alpha production. These results suggest that the varyi ng capacity to produce IL-6 and TNF-alpha may play a role in B-CLL pro gression and in clinical manifestations of the disease.