Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice

Peter Schirmacher, Malte Peters, Gennaro Ciliberto, Manfred Blessing, Johannes Lotz, Karl Hermann Meyer Zum Büschenfelde, Stefan Rose-John

Research output: Contribution to journalArticle

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Abstract

Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6- induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.

Original languageEnglish
Pages (from-to)639-648
Number of pages10
JournalAmerican Journal of Pathology
Volume153
Issue number2
Publication statusPublished - Aug 1998

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Extramedullary Hematopoiesis
Interleukin-6 Receptors
Plasmacytoma
Transgenic Mice
Hyperplasia
Interleukin-6
Membranes
Interleukin-4 Receptors
Ligands
Cytokine Receptors
Purpura
Interleukin-1 Receptors
Tumor Necrosis Factor Receptors
Interleukins
Hematopoietic Stem Cells
Plasma Cells
Hepatocytes
Necrosis
Spleen
Cytokines

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Schirmacher, P., Peters, M., Ciliberto, G., Blessing, M., Lotz, J., Meyer Zum Büschenfelde, K. H., & Rose-John, S. (1998). Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. American Journal of Pathology, 153(2), 639-648.

Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. / Schirmacher, Peter; Peters, Malte; Ciliberto, Gennaro; Blessing, Manfred; Lotz, Johannes; Meyer Zum Büschenfelde, Karl Hermann; Rose-John, Stefan.

In: American Journal of Pathology, Vol. 153, No. 2, 08.1998, p. 639-648.

Research output: Contribution to journalArticle

Schirmacher, P, Peters, M, Ciliberto, G, Blessing, M, Lotz, J, Meyer Zum Büschenfelde, KH & Rose-John, S 1998, 'Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice', American Journal of Pathology, vol. 153, no. 2, pp. 639-648.
Schirmacher, Peter ; Peters, Malte ; Ciliberto, Gennaro ; Blessing, Manfred ; Lotz, Johannes ; Meyer Zum Büschenfelde, Karl Hermann ; Rose-John, Stefan. / Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. In: American Journal of Pathology. 1998 ; Vol. 153, No. 2. pp. 639-648.
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