Interleukin-6 overexpression cannot generate serious disorders in severe combined immunodeficiency mice.
C57BL/6 human interleukin-6 (IL-6) transgenic mice develop mesangial proliferative glomerulonephritis with massive IgG1 plasmacytosis and die of renal failure in early life. To test whether the IL-6 overexpression could cause development of mesangial proliferative glomerulonephritis without plasmacytosis or promote proliferation of immature B cells that have not undergone immunoglobulin gene rearrangement, the IL-6 transgene was introduced into mice with severe combined immunodeficiency (SCID). In the immunocompetent littermate IL-6 transgenic mice, there were various symptoms such as plasmacytosis, nephropathy, anemia, and thrombocytosis, accompanied by marked increases in serum IL-6 levels as they aged. All these mice died by 25 weeks of age. In contrast, the SCID-IL-6 transgenic mice had no such abnormalities, except certain hematological changes, although the transgene was expressed in various tissues. In these mice, the serum IL-6 levels were 10- to 15-fold higher than those in the nontransgenic mice, and they remained constant throughout their lives. Furthermore, there were no signs of lymphoid development. This study demonstrates that deregulation of IL-6 expression does not stimulate cell growth or differentiation of immature B cells, and thus does not result in plasmacytosis and age-related increases in IL-6 production, and also does not generate mesangial proliferative glomerulonephritis.
Katsume
A
A
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Komakado 1-135, Gotemba-shi, Shizuoka, 412, Japan.
Miyai
T
T
Suzuki
H
H
Moriguchi
Y
Y
Kawata
H
H
Tatsumi
T
T
Suematsu
S
S
Kishimoto
T
T
Ohsugi
Y
Y
D000818:Animals; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000473:pathology
D015850:Interleukin-6