EFFECTS OF VITAMIN-D-3 AND CYCLOSPORINE-A ON HGCL2-INDUCED AUTOIMMUNITY BROWN-NORWAY RATS

Background. Mercuric chloride (HgCl2) induces a lymphoproliferative di sorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. Th is syndrome is the consequence of T cell-dependent polyclonal B cell a ctivation and autoantibody production. We have previously shown that H gCl2-induced autoimmune perturbations can be prevented in BN rats by t he administration of cyclosporin A (CsA). The most potent vitamin D-3 metabolite 1,25(OH)(2) D-3 (Vit D-3) shares certain immunomodulatory p roperties with CsA. We therefore chose to compare the effects of Vit D -3 to those of CsA in BN rats treated with HgCl2 in order to establish whether Vit D-3 either alone or in combination with CsA can attenuate an autoimmune syndrome in vivo. Methods. BN rats were treated with Hg Cl2 according to a standard protocol. Subgroups of rats were also give n CsA alone, Vit D-3 or synthetic analogues of Vit D-3 alone, or combi nations of both agents. Different doses and routes of administration w ere compared. The following markers of disease activity were evaluated : mortality, peak proteinuria, serum IgE concentrations, and renal imm unoglobulin deposition. Results. Disease activity was markedly attenua ted in all rats treated with CsA alone. Vit D-3 and certain of its syn thetic analogues administered alone also tempered the autoimmune proce ss, but to a lesser extent than did CsA. The effect of CsA alone was s o potent, that no additive or synergistic effects could be demonstrate d when CsA was administered in combination with Vit D-3. Conclusions, Despite similar described immunomodulatory effects in vitro, CsA is cl early more effective than Vit D-3 in preventing HgCl2 autoimmune disea se in BN rats. This suggests that there is a difference in the cellula r targets of these two agents in vivo, and/or a difference in the pote ncy with which HgCl2-triggered immune activation is suppressed.