S6D:7 Novel alpha-1-antitrypsin fragment as potential treatment of systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by a loss of immunologic tolerance, production of auto-antibodies and inflammatory damage in multiple organs. We have tested the effect of a novel anti-inflammatory peptide, a fragment of alpha-1-antitrypsin, termed UBE on two animal models of SLE, MRL/lpr and NZBW/F1 mice. Treatment of MRL/lpr mice with low dose of UBE (1 microgram/kg) at early stage of disease namely, 12 weeks old mice, caused significant reduction in proteinuria and hematuria. The beneficial effect of the peptide was corroborated by histological examination. Furthermore, a significant reduction in serum IL17, IL12 and anti dsDNA antibodies was observed in the UBE-treated mice. Isolated CD4 cells incubated with the peptide showed similar cytokine profile. Decreased levels of double negative CD4-CD8- and B220+cells were determined in lymph organs of UBE-treated animals. Similar effects were observed with NZBW/F1 mice, namely, the peptide (0.3 microgram/kg) caused significant reduction in proteinuria and, kidney and lung damage as determined in histopathological examination. The highly important SLE serum factor B-lymphocyte stimulator (BLyS or BAFF) was dramatically decreased in UBE-treated mice. Spleen and blood double negative CD4-CD8- and serum IL6, IP10 and MCP1 were significantly reduced in peptide-treated mice. The beneficial effects of UBE suggest this peptide as potential drug for SLE.