Expression and Production of Interleukin 4 in B-Cell Chronic Lymphocytic Leukaemia

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Abstract
Interleukin (IL) 4 is a T-cell derived pleiotropic cytokine whose properties include alterations of B-cell function. In B-cell chronic lymphocytic leukaemia (B-CLL), IL4 is involved in the mechanism of survival of the leukaemic B-cells. The present study examines the expression and production of IL4 by B- and T-lymphocytes derived from patients with B-CLL and provides evidence that IL4 is not an autocrine factor in B-CLL. Freshly isolated B-CLL cells enriched for B- and T-cells did not express mRNA for IL4 but expressed mRNA for IL4 receptor (IL4R). Activation of B-cells with phorbol ester and calcium ionophore and of T-cells with phytohaemaglutinin (PHA) upregulated IL4 mRNA expression. However phorbol ester and calcium ionophore did not affect the mean level of IL4 production by either B-CLL or normal B-cells. Furthermore, in the presence or absence of activation, the amount of IL4 synthesised by B-CLL B-cells was not significantly different than that observed with peripheral blood B-cells isolated from normal individuals (with activation: P=0.239; without activation: P=0.565). Also, there was no significant difference between normal and B-CLL B-cells in the level of cytoplasmic IL4 (P=0.47). PHA-activated enriched B-CLL T-cells produced significantly higher levels of IL4 compared to normal control T-cells (P=0.0136). In addition, in 47% of cases with B-CLL T-cells, a significant higher level of intracellular IL4 was observed (P=0.0027). The levels of production of IL4 by the T-cell-enriched preparations correlated positively with the intensity of cytoplasmic IL4 in CD4+ and CD8+ cells in tested samples (r=0.49 and r=0.76, respectively). The significant differences observed in the production of IL4 by B-CLL B- and T-lymphocytes may suggest a paracrine function of IL4 in B-CLL.