title: Successful therapy of visceral leishmaniasis with curdlan involves T-helper 17 cytokines.
abstract: The aim of this study was to evaluate and characterize the therapeutic potential of curdlan, a naturally occurring β-glucan immunomodulator, against visceral leishmaniasis, a fatal parasitic disease. Curdlan eliminated the liver and spleen parasite burden in a 45-day BALB/c mouse model of visceral leishmaniasis at a dosage of 10 mg/kg/day as determined by Giemsa-stained organ impression smears. Curdlan was associated with production of the disease-resolving T-helper (Th) 1 and Th17-inducing cytokines interleukin (IL)-6, IL-1β, and IL-23, as well as with production of Th17 cytokines IL-17 and IL-22, as determined by enzyme-linked immunosorbent assay (ELISA) and real time polymerase chain reaction (RT-PCR). Reversal of curdlan-mediated protection by anti-IL-17 and anti-IL-23 monoclonal antibodies showed the importance of Th17 cytokines. Significantly decreased production of both IL-17 and IL-22 by mice that received anti-IL-23 antibody suggested the essential role of IL-23 in Th17 differentiation. Although administration of recombinant IL-17 or IL-23 caused significant suppression of the organ parasite burden, with marked generation of interferon γ and nitric oxide (NO), effects were much faster for IL-17. These results documented that although both IL-23 and IL-17 play major roles in the antileishmanial effect of curdlan, the effect of IL-23 may occur indirectly, through the induction of IL-17 production.
authors.affiliation: Department of Biochemistry, Calcutta University, Kolkata, India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Ghosh
authors.forename: Gunjan
authors.initials: G
authors.lastname: Sharma
authors.forename: Amrita
authors.initials: A
authors.lastname: Saha
authors.forename: Susanta
authors.initials: S
authors.lastname: Kar
authors.forename: Pijush K
authors.initials: PK
authors.lastname: Das
authors.forename: Anindita
authors.initials: A
authors.lastname: Ukil
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism*; D047071:beta-Glucans / Q000494:pharmacology* / Q000627:therapeutic use; D000097043:Interleukin-22
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007371:Interferon-gamma; D007375:Interleukin-1; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; D009569:Nitric Oxide; D047071:beta-Glucans; D000097043:Interleukin-22; C038459:curdlan