The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia rodhaini in BALB/c mice.
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.
Rosenblatt-Bin
H
H
CAIR Institute, Marilyn Finkler Cancer Research Center, Bar Ilan University, Ramat Gan, Israel.
Kalechman
Y
Y
Vonsover
A
A
Xu
R H
RH
Da
J P
JP
Shalit
F
F
Huberman
M
M
Klein
A
A
Strassmann
G
G
Albeck
M
M
Sredni
B
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001404:Babesiosis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005030:Ethylenes / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000187:drug effects* / Q000502:physiology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D005030:Ethylenes; D007375:Interleukin-1; D012333:RNA, Messenger; D018664:Interleukin-12; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D007371:Interferon-gamma