The soluble form of interleukin-6 receptor modulates cell proliferation by acute myeloblastic leukemia blast cells

As interleukin-6 (IL-6) has been shown to have diverse effects on blast cell growth in acute myeloblastic leukemia (AML), and as a soluble (s) form of IL-6 receptor (IL-6R) agonizes IL-6 effects in many cell types, we investigated whether sIL-6R was able to modulate clonogenic blast cell growth in AML. The proliferation responses of eight autonomously growing AML cell lines and eight primary AML blast cell samples were compared with their IL-6 and sIL-6R expression. Only three of the 16 AML samples were influenced by IL-6, two of them being stimulated and one inhibited by it. The sIL-6R-induced responses were more frequent, however, and, in contrast to those by IL-6, always stimulatory: clonogenic cell growth in six of the 16 AML samples was stimulated by sIL-6R treatment. All the cell lines and four of the seven primary blast cell samples analyzed expressed IL-6, and the expression was associated with unresponsiveness to exogenous IL-6. sIL-6R was also frequently expressed by AML cells: only one of the samples was negative for it. However, there was no correlation between sIL-6R expression and the responsiveness of cells to exogenous sIL-6R. The work presented here shows that sIL-6R is able to stimulate blast cell growth in AML. As AML blast cells are provided by exogenous IL-6 and sIL-6R in a bone marrow environment, and as many of them also express IL-6 and sIL-6R themselves in vitro, it is possible that signaling through the IL-6/sIL-6R system plays a role in maintaining their growth also in vivo.