1. The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia rodhaini in BALB/c mice
- Author
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Benjamin Sredni, Ji-Ping Da, F. Shalit, Yona Kalechman, Ren-He Xu, Gideon Strassmann, Michael Albeck, Ami Vonsover, Hanna Rosenblatt-Bin, Avraham Klein, and M. Huberman
- Subjects
Male ,Antiparasitic ,medicine.drug_class ,Immunology ,Biology ,BALB/c ,Interferon-gamma ,Mice ,Downregulation and upregulation ,Adjuvants, Immunologic ,Immunity ,Babesiosis ,medicine ,Parasite hosting ,Macrophage ,Animals ,Secretion ,RNA, Messenger ,Messenger RNA ,Mice, Inbred BALB C ,Ethylenes ,Th1 Cells ,biology.organism_classification ,Molecular biology ,Interleukin-12 ,Cytokines ,Interleukin-1 - Abstract
The immunomodulator AS101 has been previously shown to confer protection upon BALB/c mice infected with the intraerythrocytic parasite Babesia rodhaini (B. rodhaini). The present study focuses on the effect of AS101 administration on the acute phase of babesial infection where T helper cell subset patterns-TH1/TH2-were assessed in heavily infected mice. Secretion of cytokines of the TH1 subset (IL-2, IFN-gamma, IL-12) and of the TH2 subset (IL-10, IL-4) as well as TGF-beta was measured following the administration of AS101 2 weeks before parasite infection. Our results demonstrate that the parasites suppress IL-2 protein and IL-12 mRNA and that AS101 upregulates their secretion: IL-2, 8 u/ml vs 34 u/ml, respectively; IFN-gamma protein, 2370 pg/ml vs 4777 pg/ml, respectively. Conversely, babesial infection results in the upregulation of IL-10 and IL-4 proteins and TGF-beta transcripts, whereas AS101 downregulates their production: IL-10, 1800 pg/ml vs 360 pg/ml, respectively; IL-4, 58.3 pg/ml vs 24.5 pg/ml, respectively. A possible escape mechanism induced by B. rodhaini is suggested, starting with IL-10 inhibition of macrophage activities leading to a suppression of the TH1 response and of IL-2 in particular. It is therefore possible that AS101 may protect infected mice by activating cellular-mediated immunity and concurrently balancing the TH subset responses. It is suggested that AS101 may be effective as an antiparasitic drug.
- Published
- 1998