Interleukin-6 and the soluble interleukin-6 receptor induce stem cell factor and Flt-3L expression in vivo and in vitro

Objective. We recently established transgenic animals expressing either interleukin-6 (IL-6) or the soluble IL-6 receptor (sIL-6R) alone, or both components, IL-6 and the sIL-6R, in the liver. This animal model demonstrated that the expression of IL-6 in combination with its sIL-6R led to extramedullary expansion of hematopoietic progenitor cells in the spleen and liver. Materials and Methods. We studied other relevant hematopoietic cytokines involved in the IL-6/sIL-6R-induced stimulation of hematopoiesis. Results, Using immunohistochemistry, we show;ed that cell-associated stem cell factor (SCF) and Flt-3L expression were upregulated in liver and spleen only in double transgenic mice but not in IL-6 or sIL-6R single transgenic animals, Moreover, on murine NIH/3T3 fibroblasts and on human primary forskin fibroblasts, stimulation with the IL-6/sIL-6R complex, and to a lesser extent with IL-6 alone, led to induction of cellular SCF and Flt-3L expression, When human HTB-158 fibroblasts were stimulated with the IL-6/sIL-6R complex and subsequently cocultured with human umbilical cord CD34(+) cells, a significant upregulation in colony growth was found. Conclusions. We showed that IL-6 in combination with its soluble receptor stimulates cellular SCF and Flt-3L expression in vivo and in vitro, Cellular upregulation of SCF and Flt-3L, by IL-6/sIL-6R might be used for the development of new stroma cell systems for ex vivo expansion of hematopoietic progenitor cells. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.