POTENTIAL ROLE FOR IL-5 AND IL-6 IN ENHANCED IGA SECRETION BY PEYERS PATCH CELLS ISOLATED FROM MICE ACUTELY EXPOSED TO VOMITOXIN

Dietary exposure to vomitoxin (VT) results in hyperelevated serum IgA and IgA nephropathy in mice. To assess the possible role of cytokines in this IgA dysregulation, the effects of a single oral exposure in B6 C3F1 male mice to 0, 5 or 25 mg/kg BW VT on production of IgA and cyto kines in Peyer's patch CPP and spleen cell cultures were evaluated. Ig A levels were increased significantly in PP cell cultures prepared fro m mice at 2 or 24 h after oral exposure to VT and subsequently stimula ted with phorbol myristate acetate (PMA) and ionomycin (ION) or with l ipopolysaccharide (LPS). Significant effects on IgA production were no t observed in spleen cell cultures. Since cytokines such as IL-2, IL-4 , IL-5 and IL-6 have been shown to promote IgA production, the effect of the same VT exposure regimen on secretion of these mediators was de termined in PP and spleen cultures. Supernatant IL-2 and IL-4 levels w ere unaffected by the prior treatment of animals with VT. In contrast, IL-5 levels were increased significantly in 7-day PP cell cultures ob tained 2 h after VT exposure both with and without PMA + ION exposure but not in other cultures. IL-6 levels were increased significantly in LPS-treated cultures prepared from PP at 2 and 24 h following exposur e to VT. IL-6 levels were also elevated significantly in both PMA + IO N or LPS treated cultures from spleen isolated at 2 h but not 24 h pos t VT exposure. To determine whether IL-5 or IL-6 play a role in IgA hy perelevation in vitro, PP and spleen cells from mice obtained 2 h afte r exposure to 25 mg/kg VT were cultured in the presence of neutralizin g cytokine antibodies (Abs) and IgA production was monitored. Consiste nt with IL-5's previously documented role in IgA production, anti-IL-5 decreased IgA levels to background in cultures of both control and VT -exposed PP or spleen cells in the presence of either PMA + ION or LPS . Similar results were seen with addition of anti-IL-6. IgA levels wer e decreased to a lesser extent in PP cells cultured with LPS and in sp leen cells cultured with PMA + ION from VT-exposed mice to which anti- IL-2 Ab was added. Thus, the potential for enhanced IgA production exi sts in lymphocytes as early as 2 h and as late as 24 h after a single oral exposure to VT and this may be related to the increased capacity to secrete helper cytokines of T cell and macrophage origin. Taken tog ether, the results suggest that the superinduction of cytokine express ion may, in part, be responsible for upregulation of IgA secretion in mice exposed orally to VT. (C) 1997 Elsevier Science Ireland Ltd.