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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 and G Ciliberto
Department of Genetics of IRBM P. Angeletti, Pomezia, Roma, Italy.
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 alpha 2- and
beta-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.
Volume 83,
Issue 9,
pp. 2570-2579,
05/01/1994
Copyright © 1994 by The American Society of Hematology
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