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Malte Peters^*, Peter Schirmacher, Jutta Goldschmitt, Margarete Odenthal, Christian Peschel, Elena Fattori^||, Gennaro Ciliberto^||, Hans-Peter Dienes^¶, Karl-Hermann Meyer zum Büschenfelde^*, and Stefan Rose-John^*

From the ^* I. Department of Medicine, Section of Pathophysiology; Institute of Pathology; III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ^|| Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ^¶ Institute of Pathology, University of Cologne, 51123 Cologne, Germany

Soluble cytokine receptors modulate the activity of their cognate ligands. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lacking the specific IL-6R. To investigate the function of the IL-6–sIL-6R complex in vivo and to discriminate the function of the IL-6–sIL-6R complex from the function of IL-6 alone, we have established a transgenic mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6–sIL-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 single-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 signal 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 progenitor cells in vivo and in vitro.

¹ Abbreviations used in this paper: CNTF, ciliary neurotrophic factor; CT-1, cardiotrophin-1; LIF, leukemia inhibitory factor; OSM, oncostatin M; PEPCK, phosphoenolpyruvate carboxykinase; sIL-6R, soluble interleukin-6 receptor; TNF-R, tumor necrosis factor receptor.

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