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

Background. Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. This syndrome is the consequence of T cell-dependent polyclonal B cell activation and autoantibody production. We have previously shown that HgCl2-induced autoimmune perturbations can be prevented in BN rats by the administration of cyclosporin A (CsA). The most potent vitamin D-3 metabolite 1,25(OH)(2) D-3 (Vit D-3) shares certain immunomodulatory properties 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 HgCl2 according to a standard protocol. Subgroups of rats were also given CsA alone, Vit D-3 or synthetic analogues of Vit D-3 alone, or combinations of both agents. Different doses and routes of administration were compared. The following markers of disease activity were evaluated: mortality, peak proteinuria, serum IgE concentrations, and renal immunoglobulin deposition. Results. Disease activity was markedly attenuated in all rats treated with CsA alone. Vit D-3 and certain of its synthetic analogues administered alone also tempered the autoimmune process, but to a lesser extent than did CsA. The effect of CsA alone was so potent, that no additive or synergistic effects could be demonstrated when CsA was administered in combination with Vit D-3. Conclusions, Despite similar described immunomodulatory effects in vitro, CsA is clearly more effective than Vit D-3 in preventing HgCl2 autoimmune disease in BN rats. This suggests that there is a difference in the cellular targets of these two agents in vivo, and/or a difference in the potency with which HgCl2-triggered immune activation is suppressed.