The role of helminth treatment in autoimmune diseases is constantly growing. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network.
This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone).
Lupus-prone NZBxW/F1mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5mg/body weight) or PBS (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dL, was established. Levels of anti-dsDNA autoantibodies were evaluated by ELISA, splenic cytokines were measured in-vitro, and the kidney microscopy was analyzed following staining.
TPC and MP treatments significantly improved lupus nephritis and prolonged survival in NZBxW/F1 mice. TPC-treated mice showed a significantly decreased level of proteinuria (p<0.001) and anti-dsDNA antibodies (p<0.001) as compared to PBS-treated mice. Moreover, TPC and MP inhibited the production of the pro-inflammatory cytokines IFN-γ, IL-1β, and IL-6 (p<0.001) and enhanced expression of the anti-inflammatory cytokine IL-10 (p<0.001). Finally, microscopy analysis of the kidneys demonstrated that TPC-treated mice maintained normal structure equally to MP-treated mice.
This data indicates that the small molecule named TPC hinders lupus development in genetically lupus-prone mice equally as methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.