Role of gender and strain in vomitoxin-induced dysregulation of IgA production and IgA nephropathy in the mouse.

Abstract

Prolonged dietary exposure of female B6C3F1 mice to the trichothecene vomitoxin results in hyperproduction of immunoglobulin A (IgA) with a concurrent immunopathology that mimics human IgA nephropathy. To assess the role of gender and strain in the mouse model, semipurified AIN-76A diet containing 25 ppm vomitoxin was fed to B6C3F1 male mice and to B6C3F1, BALB/c, C3H/HeN, C3H/HeJ, and C57BL/6 female mice for 8 wk, and immunopathologic indicators of IgA nephropathy were compared to mice fed clean diet. At the cessation of the experiment, all treatment groups weighed less than respective controls. Serum IgA was increased in male and female B6C3F1 mice as well as in C3H/HeJ, C57BL/6, and BALB/c female mice compared to corresponding controls. Serum IgA levels were two- to sixfold higher in B6C3F1 male treatment animals compared to female treatment groups from all strains. In contrast, at wk 8 serum IgG levels were unaffected or decreased, and serum IgM was decreased in all groups at wk 8. There was a trend toward increased IgA production by Peyer's patch (PP) lymphocytes isolated from treatment mice as compared to controls in all groups except the C3H/HeJ mice. Notably, IgA levels were 18-fold higher in B6C3F1 male treatment PP cultures than in B6C3F1 female treatment cultures. Hematuria was significantly greater in treatment mice than respective controls at both wk 4 and 8. Increased mesangial IgA deposition was also detectable in all treatment groups except the C57BL/6 mouse. The results suggested that the male B6C3F1 mouse and the five strains of female mice exhibited many of the immunopathologic effects found in IgA nephropathy and that IgA elevation was more marked in male B6C3F1 than female B6C3F1 mice.