Suppression of systemic lupus erythematosus disease in mice by oral administration of kidney extract.

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of antibodies reactive with a variety of self and non-self antigens. A number of immunomodulatory therapies have been investigated for the disease process. Intragastric administration of low dose kidney extract (KE) three times weekly for 5 weeks and then weekly until 6 months of age in SLE mice, showed decreased anti-dsDNA antibody levels, less kidney damage and significantly prolonged survival compared with control phosphate buffered saline (PBS)-fed mice. The KE-fed mice also exhibited reduced T cell proliferative response to KE in comparison with PBS-fed controls. Serum isotype distribution of the anti-dsDNA antibodies revealed a marked reduction of IgG1 and IgG3 responses in the KE-fed mice. While the renal inflammatory cell infiltration and expression of interleukin-4 (IL-4) and IL-10 were markedly suppressed, no local enhancement of transforming growth factor-beta (TGF-beta) was detected. Oral administration of low dose KE, however, upregulated expression of IL-2, IFN-gamma and TNF-alpha in the kidneys and suppressed glomerulonephritis. These findings suggest that oral KE affects the disease process in SLE and raise the possibility that oral administration of KE or other potential autoantigens may provide a new approach for the treatment of SLE.