Long-term consequences of interleukin-6 overexpression in transgenic mice.
With the aim of using interleukin-6 (IL-6)-inducible promoters to express transgenes, we investigated the long-term consequences of high levels of IL-6 in mice. As a first step, we generated transgenic mice constitutively expressing the murine IL-6 at a level sufficient to induce IL-6-responsive genes. These mice were analyzed with respect to the indirect and direct consequences of elevated IL-6 expression over a time period of about 2 years. Although biologically active IL-6 was expressed from the transgene and different alterations could be documented (less immature B cells in bone marrow, expression of IL-6-inducible liver genes), the mice appeared healthy and could easily be used for breeding. Only in mice older than 18 months did we find a high incidence of lymphomas associated with different tissues. These results indicate that the side effects of long-term treatment with IL-6 are relatively moderate, and that IL-6 might be used to mediate the expression of heterologous genes in the context of functional studies.
Woodroofe
C
C
European Molecular Biology Laboratory, Heidelberg, Germany.
Müller
W
W
Rüther
U
U
D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000235:genetics* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000139:chemically induced; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000187:drug effects*
D000209:Acute-Phase Proteins; D015850:Interleukin-6