Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice

E. Fattori, C. Della Rocca, P. Costa, M. Giorgio, B. Dente, L. Pozzi, G. Ciliberto

Research output: Contribution to journalArticle

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Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been postulated as playing a role in the pathogenesis of multiple myeloma, chronic autoimmune diseases, and alcoholic liver cirrhosis. We generated transgenic mice carrying a fusion between the mouse metallothionein-I (MT-I) gene promoter and the human IL-6 cDNA. MT-I/IL-6 transgenics express IL-6 constitutively in the liver and secrete the cytokine in the blood. They show initially activation of acute-phase response genes and accumulation of α2- and β- globulins in the plasma, which is followed by polyclonal hypergammaglobulinemia. MT-I/IL-6 transgenics die between 12 to 20 weeks of age. Histologic examination of transgenic animals at different ages and after necropsy showed, as expected from previous studies of IL-6 disregulation in vivo, an increase in the number of megakaryocytes in the spleen and bone marrow and, at later stages, IgG plasmacytosis in the spleen, lymph nodes, and thymus. However, no plasma cell infiltration was detected in other organs. The distinguishing feature of MT-I/IL-6 transgenics is the development of a progressive kidney pathology, in which the initial membranous glomerulonephritis is followed by focal glomerulosclerosis and finally by extensive tubular damage that reproduces the damage observed in patients at terminal stages of multiple myeloma (myeloma kidney). The pathogenetic role of IL-6 overproduction and of the resulting serum protein overload in the kidney damage is discussed.

Original languageEnglish
Pages (from-to)2570-2579
Number of pages10
JournalBlood
Volume83
Issue number9
Publication statusPublished - May 1 1994

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Transgenic Mice
Interleukin-6
Kidney
Metallothionein
Multiple Myeloma
Liver
Spleen
Genes
Cytokines
Hypergammaglobulinemia
Plasmas
Thymus
Focal Segmental Glomerulosclerosis
Alcoholic Liver Cirrhosis
Membranous Glomerulonephritis
Acute-Phase Reaction
Genetically Modified Animals
Megakaryocytes
mouse interleukin-6
Globulins

ASJC Scopus subject areas

  • Hematology

Cite this

Fattori, E., Della Rocca, C., Costa, P., Giorgio, M., Dente, B., Pozzi, L., & Ciliberto, G. (1994). Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. Blood, 83(9), 2570-2579.

Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. / Fattori, E.; Della Rocca, C.; Costa, P.; Giorgio, M.; Dente, B.; Pozzi, L.; Ciliberto, G.

In: Blood, Vol. 83, No. 9, 01.05.1994, p. 2570-2579.

Research output: Contribution to journalArticle

Fattori, E, Della Rocca, C, Costa, P, Giorgio, M, Dente, B, Pozzi, L & Ciliberto, G 1994, 'Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice', Blood, vol. 83, no. 9, pp. 2570-2579.
Fattori E, Della Rocca C, Costa P, Giorgio M, Dente B, Pozzi L et al. Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. Blood. 1994 May 1;83(9):2570-2579.
Fattori, E. ; Della Rocca, C. ; Costa, P. ; Giorgio, M. ; Dente, B. ; Pozzi, L. ; Ciliberto, G. / Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. In: Blood. 1994 ; Vol. 83, No. 9. pp. 2570-2579.
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