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.
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 microg/mouse), plasmid (100 microg/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.
Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, 1677-1, Yoshida, Yamaguchi, 753-8515, Japan. hayasi@yamaguchi-u.ac.jp
Toshiharu
T
Hayashi
Keiko
K
Hasegawa
Yuji
Y
Sasaki
Takashi
T
Mori
Cie
C
Adachi
Ken
K
Maeda
D000818:Animals; D005260:Female; D051379:Mice; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004247:DNA / Q000235:genetics / Q000494:pharmacology; D005921:Glomerulonephritis / Q000517:prevention & control; D015847:Interleukin-4 / Q000235:genetics / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008815:Mice, Inbred Strains; D010957:Plasmids; D011994:Recombinant Proteins / Q000627:therapeutic use; D014162:Transfection
D004247:DNA; D015847:Interleukin-4; D011994:Recombinant Proteins