EXTRAMEDULLARY EXPANSION OF HEMATOPOIETIC PROGENITOR CELLS IN INTERLEUKIN (IL)-6-SIL-6R DOUBLE TRANSGENIC MICE

Soluble cytokine receptors modulate the activity of their cognate liga nds. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lac king the specific IL-6R. To investigate the function of the IL-6sIL-6R complex in vivo and to discriminate the function of the IL-6sIL-6R co mplex from the function of IL-6 alone, we have established a transgeni c mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R wer e generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6sIL-6R mice was a dramatic increase of extramedullary hematopoietic progenitor cells in liver and spleen but not in the bone marrow. In IL-6 single-transgenic mice and sIL-6R sin gle-transgenic mice no such effects were observed. The high numbers of hematopoietic progenitor cells were reflected by a strong increase of peripheral blood cell numbers. Therefore, activators of the gp130 sig nal transducer like the IL-6-IL-6R complex may represent most powerful stimulators for extramedullary hematopoietic progenitor cells. gp130 activators may become important for the expansion of hematopoietic pro genitor cells in vivo and in vitro.