title: Preventive effect of pidotimod on reactivated toxoplasmosis in mice.
abstract: 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.
authors.affiliation: The Key Laboratories of Parasitology and Zoonoses Anhui and Department of Parasitology, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Huo
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Zhao-Wu
authors.initials: ZW
authors.lastname: Chen
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.forename: Xiu-Cai
authors.initials: XC
authors.lastname: Xu
authors.forename: Ai-Mei
authors.initials: AM
authors.lastname: Zhang
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Luo
authors.forename: Yuan-Hong
authors.initials: YH
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Cai
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
authors.forename: Fang-Li
authors.initials: FL
authors.lastname: Lu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Shen
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D053778:Thiazolidines / Q000627:therapeutic use*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D053778:Thiazolidines; C064893:pidotimod; D003520:Cyclophosphamide; D011761:Pyrrolidonecarboxylic Acid