Effect of adamantylamide dipeptide on reinfection resistance after primary infection eradication in experimental Schistosomiasis mansoni.
The immunomodulatory effect of adamantylamide dipeptide (AdDP) was tested in Schistosoma mansoni-infected challenged mice and infected praziquantel-treated (2 x 500 mg/kg) challenged animals. In AdDP-treated mice, the drug was given 58 days post infection of mice with 120 S. mansoni cercariae, challenged with 240 cercariae one day after treatment, while in praziquantel-treated mice, the drug was given 44 days post infection, two weeks post treatment (58 days post infection) they were given AdDP in the same dose and one day later challenged with the same cercarial load. AdDP increased the resistance against reinfection (90.3% vs. 83.5% in infected challenged control). The significant increase in resistance against reinfection was accompanied by significant increase in the percentage of lymphocytes forming EAC rosettes. Mice cured of their primary infection by praziquantel showed a significant reduction in percent resistance, hepatic granuloma size and intragranulomal Thy+ 1,2 and Lyt+ 1 T cells. In mice treated with both praziquantel and AdDP, resistance to reinfection was significantly higher than in mice treated with praziquantel only (89.29% vs. 62.13%) reaching a level comparable to that recorded in infected-challenged controls. Meanwhile granuloma size was not significantly different from that in the infected-challenged controls with a significant rise in Lyt+ 1 T cells. Data may suggest a role for granuloma as a mechanical obstacle and/or as a T cell-mediated reaction in maintenance of resistance to reinfection. A role for B lymphocytes should be considered as the rise of percent resistance to reinfection in mice treated with AdDP alone was accompanied by a significant increase in the percentage of B lymphocytes forming EAC rosettes. Moreover, findings may suggest the use of AdDP together with specific chemotherapy in endemic areas where reinfection and repeated treatment with its consequences are of common occurrence.
Botros
S
S
Theodor Bilharz Research Institute, Cairo, Egypt.
Mahmoud
S
S
Hassan
S
S
Ibrahim
A
A
Zidek
Z
Z
Masek
K
K
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000547:Amantadine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000980:Antiplatyhelmintic Agents / Q000627:therapeutic use; D004151:Dipeptides / Q000627:therapeutic use*; D004351:Drug Resistance; D006099:Granuloma / Q000469:parasitology; D007111:Immunity, Cellular / Q000187:drug effects; D008099:Liver / Q000469:parasitology; D008214:Lymphocytes / Q000469:parasitology; D051379:Mice; D008815:Mice, Inbred Strains; D011223:Praziquantel / Q000627:therapeutic use; D051381:Rats; D012008:Recurrence; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D012556:Schistosomicides / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000980:Antiplatyhelmintic Agents; D004151:Dipeptides; D012556:Schistosomicides; D011223:Praziquantel; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine