The Tolerogenic Peptide, hCDR1, Down-Regulates the Expression of Interferon-a in Murine and Human

Background: The tolerogenic peptide, hCDR1, ameliorated manifestations of systemic lupus erythematosus (SLE) via the immunomodulation of pro-inflammatory and immunosuppressive cytokines and the induction of regulatory T cells. Because type I interferon (IFN-a) has been implicated to play a role in SLE pathogenesis, we investigated the effects of hCDR1 on IFN-a in a murine model of SLE and in human lupus. Methodology/Principal Findings: (NZBxNZW)F1 mice with established SLE were treated with hCDR1 (10 weekly injections). Splenocytes were obtained for gene expression studies by real-time RT-PCR. hCDR1 down-regulated significantly IFN-a gene expression (73 % inhibition compared to vehicle treated mice, p = 0.002) in association with diminished clinical manifestations. Further, hCDR1 reduced, in vitro, IFN-a gene expression in peripheral blood mononuclear cells (PBMC) of 10 lupus patients (74 % inhibition compared to medium, p = 0.002) but had no significant effects on the expression levels of IFN-a in PBMC of primary anti-phospholipid syndrome patients or of healthy controls. Lupus patients were treated for 24 weeks with hCDR1 (5) or placebo (4) by weekly subcutaneous injections. Blood samples collected, before and after treatment, were frozen until mRNA isolation. A significant reduction in IFN-a was determined in hCDR1 treated patients (64.4 % inhibition compared to pretreatment expression levels, p = 0.015). No inhibition was observed in the placebo treated patients. In agreement, treatment with hCDR1 resulted in a significant decrease of disease activity. IFN-a appears to play