As one of food-borne
parasitic diseases,
toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic
dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of
pidotimod as a preventive treatment, we used a murine model of reactivated
toxoplasmosis with
cyclophosphamide (CY)-induced immunosuppression.
Pidotimod administration significantly restored the
body weight and spleen organ index, increased survival time (from 70 to 90%), and decreased the
parasitemia (from 80 to 35%) of CY-induced mice with reactivated
toxoplasmosis.
Cytokine profiles and CD4(+) T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that
pidotimod treatment resulted in a significant upregulation of pro-inflammatory
cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46%) after CY induction in infected mice. Additionally, histological findings and parasite
DNA quantification revealed that mice administered with
pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that
pidotimod significantly restored
concanavalin A-induced splenocyte proliferation and pro-inflammatory
cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of
pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of
pidotimod on reactivated
toxoplasmosis.