Interleukin-4 (IL-4) inhibits proliferation and spontaneous cytokine release by chronic lymphocytic leukaemia cells.

Previous studies have shown that interleukin-4 (IL-4) may have both stimulatory and inhibitory effects on the growth of normal and malignant B-cells in vitro. We studied the effects of IL-4 on tumour necrosis factor (TNF) induced and spontaneous proliferation (3H-TdR incorporation) and spontaneous release of TNF and interleukin-6 (IL-6) by purified B-cell chronic lymphocytic leukaemia (CLL) cells in vitro. TNF (100 U/ml) increased 3H-TdR uptake in cells to 700 +/- 302% of control (mean +/- S.E., n = 9, p = 0.033). Recombinant IL-4 (10 ng/ml) consistently inhibited DNA synthesis in all CLL patients studied. When added at the start of 5 day cultures, IL-4 inhibited both spontaneous (41 +/- 17% inhibition, n = 3) and TNF induced (46 +/- 5% inhibition, n = 9, p = 0.01) 3H-TdR uptake. Similar results were obtained when IL-4 was added after 48 h of culture. This effect of IL-4 was dose dependent. Inhibition was not related to clinical stage. IL-4 (whether added at T0 or T48h) also inhibited spontaneous release of TNF and IL-6 measured at 48 and 120 h. TNF and IL-4 had no consistent effect on normal cord blood CD5+ B-cells. These data show that IL-4 has inhibitory effects on B-CLL DNA synthesis and also inhibits spontaneous release of IL-6 and TNF in vitro. IL-4 may have a role in vivo in reducing proliferation in these B-cell malignancies by inhibiting potential autocrine growth loops.