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NDT Advance Access originally published online on July 31, 2007
Nephrology Dialysis Transplantation 2007 22(11):3131-3138; doi:10.1093/ndt/gfm465
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice

Toshiharu Hayashi1, Keiko Hasegawa1, Yuji Sasaki1, Takashi Mori1, Cie Adachi1 and Ken Maeda2

1Laboratories of Veterinary Pathology and 2Veterinary Microbiology, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan.

Correspondence and offprint requests to: T. Hayashi, Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, 1677-1, Yoshida, Yamaguchi, 753-8515, Japan Email: hayasi{at}yamaguchi-u.ac.jp



  Abstract

Background. T helper (Th)1/Th2 balance determines the direction of some kinds of autoimmune diseases. Th1 cytokines, especially interferon (IFN)-{gamma} has been proven important in the pathogenesis in lupus. The present study examined the effects of administration of interleukin (IL)-4 (Th2 cytokine) expressing plasmid DNA (IL-4pDNA) on the development of glomerulonephritis and survival in lupus-prone female NZB x NZW (B/W)F1 mice.

Methods. B/WF1 mice were administrated intraperitoneally either with IL-4pDNA (100 µg/mouse), plasmid (100 µg/mouse) or saline at 4 and 6 weeks of age and at 4 week intervals from 8 to 32 weeks of age.

Results. Compared to the saline and plasmid groups (controls), the IL-4pDNA-treatment drastically delayed the development of glomerulonephritis with deposits of IgG2a and C3 leading to excretion of urine protein, and prolonged survival. Clinical improvement was associated with the reduction in productions of IgG anti-dsDNA autoantibody. Also, compared to the other two controls the IL-4pDNA-treatment reduced production of IFN-{gamma} and increased IL-4 production from splenic cells.

Conclusions. The present study suggests that systemic IL-4pDNA administration may delay lupus onset by suppressed IFN-{gamma} production due to shifting from Th1 to Th2 responses.

Keywords: B/WF1 mice; IFN-{gamma}; IL-4; IL-4 expressing plasmid; lupus nephritis; survival; Th1/Th2 balance

The authors wish it to be known that, in their opinion, the first two authors contributed equally to this work.

Received for publication: 20. 3.07
Accepted in revised form: 19. 6.07


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