Effect of treatment with free and liposomized albendazole on selected immunological parameters and cyst growth in mice infected with Echinococcus multilocularis.
Selected immunological parameters in healthy mice and mice infected with Echinococcus multilocularis and the effect of free and liposomized albendazole (lip.ABZ) upon these parameters in relation to the reduction of parasite growth were investigated over 26 weeks. Proliferative response of splenic T and B lymphocytes, number of CD4+ and CD8+ spleen T cell subpopulations, serum concentration of IFN-gamma and IL-5, and generation of superoxide anion (O2-) by peritoneal macrophages were the chosen parameters. Both drug forms were given to mice at a dose of 10 mg kg(-1) twice a week from week 4 to week 10 post infection (p.i.) (6 weeks in total). The reduction of cyst growth after treatment with ABZ and lip.ABZ was similar up to week 4 after last dose, but the parasitostatic effect of lip.ABZ lasted 4 weeks longer than the effect of free drug. After administration of both drug forms, the proliferative responses of T and B cells were restored, and also the number of CD4+ and CD8+ increased markedly. In lip.ABZ-treated mice, stimulation of mentioned lymphocyte parameters, except that of CD8+ numbers, persisted for longer period than after ABZ therapy, where values peaked at week 12 p.i., then declined more rapidly. A very strong stimulatory effect was seen on B lymphocytes during the period of lip.ABZ administration, although interestingly, numbers of CD8+ cells were higher in free ABZ-treated group. Low concentrations of IFN-gamma (Th1 response) were present in infected, untreated mouse serum. Only moderate IFN-gamma elevation was observed after treatment with free ABZ. A profound increase of its concentration was seen shortly after administration of lip.ABZ, and persisted until the experiment ended. In infected untreated mice, concentration of IL-5 (Th2 response) was highest on week 2 p.i. Significantly more IL-5 was recorded in serum of mice treated with free ABZ treatment than with lip.ABZ from week 12 to 18 p.i. (weeks 2-8 after the last dose). After the initial increase of superoxide anions (weeks 4-11 p.i.), generation of O2- by peritoneal macrophages was gradually inhibited by E. multilcoularis infection. In general, treatment abolished this suppression and macrophages from lip.ABZ-treated mice produced elevated amounts of O2- over a longer period than macrophages from ABZ-treated mice. Our data indicate that anthelmintic potency of ABZ could be increased after incorporation into liposomes, not only because of improved pharmacokinetics and consequent bioavailability, but also because of significant stimulation of Th1-type cytokine IFN-gamma response and effector macrophage functions.
Dvoroznáková
Emília
E
Parasitological Institute of the Slovak Academy of Sciences, Hlinkova 3, 04001 Kosice, Slovak Republic.
Hrcková
Gabriela
G
Borosková
Zora
Z
Velebný
Samuel
S
Dubinský
Pavol
P
D015766:Albendazole / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D004443:Echinococcosis / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D048210:Echinococcus multilocularis / Q000187:drug effects / Q000254:growth & development*; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000871:Anthelmintics; D015848:Interleukin-5; D008081:Liposomes; D013481:Superoxides; D007371:Interferon-gamma; D015766:Albendazole