Regulatory effect of recombinant interleukin (il) 3 and il 4 on cytokine gene expression of bone marrow and peripheral blood mononuclear cells

Abstract

This study shows that both recombinant human interleukin (rhIL)3 and rhIL4 induced proliferation in bone marrow (BM) cells of myelogenous leukemia patients in a manner similar to that reported using normal BM cells. However, we additionally found that these cytokines also influenced expression of other cytokines. Namely, using a reproducible dot blot hybridization technique we observed on the one hand that BM cells were capable of constitutively expressing low levels of cytokine mRNA coding for IL3, IL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF and IL 1 beta, and on the other hand that in normal peripheral blood mononuclear cells rhIL4 inhibited mRNA expression coding for GM-CSF, G-CSF, IL3 and IL 1 beta, while IL4 mRNA and 28S rRNA was not affected. In contrast, rhIL3 marginally enhanced mRNA coding for IL3, GM-CSF, G-CSF and IL 1 beta and counteracted the inhibitory effect of IL4. In long-term cultures rhIL3 and rhIL4 had no significant effect on spontaneous cytokine gene expression of myelogenous leukemia-derived peripheral blood or BM cells, but made these cells more sensitive for subsequent stimulation with different polyclonal stimuli. Thus, IL3 and IL4 already modulate cytokine gene expression during the initiation of cell culture and differentiate BM cells into populations of cells which are capable of responding with an enhanced cytokine gene expression after polyclonal stimulation.