Purpose In this work we analyzed the therapeutic potential of a natural compound, Patemine A (PatA) to treat SLE. Pat A is an inhibitor of the eIF4 complex, involved in the translation initiation process, with immunosuppressive properties that has been tested successfully in cancer mouse models.
Methods To evaluate Pat A efficiency in SLE we used the BXSB.Yaa lupus model. In this strain the presence of Yaa in males results in autoimmune disease manifestations, renal failure, and a mortality rate of 60% by 20 weeks of age. BXSB.Yaa males were treated with PatA administered intraperitoneally 3 times per week for 8 weeks starting at the initial stage of disease (12 weeks). Sera was collected every three weeks to follow disease progression and at final point (20 weeks) we performed serological analysis (cytokines and autoantibodies), flow cytometry on spleen, kidney histological and functional assays and behavioral tests to evaluate neurological signs of the disease.
Results Pat A treatment increased survival rates and reduced circulating levels of proinflammatory cytokines and autoantibodies in the BXSB.Yaa lupus model. Kidney function was also improved in the animal that received Pat A with no major changes at the histological level. Treated mice also showed an improvement on cognitive function (learning/memory, and depression) together with a reduction of proinflammatory cytokines locally in the hippocampus.
Conclusions These data suggest that translation inhibition improves disease signs at the immunological and neurological level opening a new line of research based on translation inhibition to treat lupus and other autoimmune diseases.
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