NDLI: Cyclosporin A-mediated killing of Leishmania major by macrophages is independent of reactive nitrogen and endogenous TNF-α and is not inhibited by IL-10 and 13

Content Provider	Springer Nature Link
Author	Meißner, Udo Jüttner, Stefan Röllinghoff, Martin Gessner, André
Copyright Year	2003
Abstract	Murine macrophages were treated with various doses of cyclosporin A (CsA) to enhance the killing of Leishmania major parasites. CsA reduced the rate of infected cells from 75% in non-treated controls to less than 15% with 1µg CsA/ml in a dose-dependent manner. The leishmanicidal effect was also observed when CsA was added 48 h after the infection of macrophages. In contrast, FK506, another structural non-related immunosuppressive drug with antiparasitic activities, showed no effect on the ability of macrophages to kill intracellular Leishmania parasites. Since nitric oxide has been identified as a key molecule for the leishmanicidal function of macrophages, we analyzed the role of this molecule. There was no influence on the leishmanicidal effect of CsA when L-N-(1-iminoethyl)lysine, a potent and selective inhibitor of mouse inducible nitric oxide synthase, was added. Furthermore, the presence of the macrophage-inhibiting cytokines interleukin (IL)-10 and IL-13 simultaneously or prior to CsA did not inhibit leishmania killing, while both cytokines completely prevented parasite killing by macrophages activated with gamma interferon and tumor necrosis factor (TNF). CsA was fully active on macrophages from TNF-receptor p55 knockout mice arguing against autocrine activation by TNF. We therefore conclude that the antileishmanial effect of CsA is independent of effector mechanisms employed by macrophage-activating cytokines.
Starting Page	221
Ending Page	227
Page Count	7
File Format	PDF
ISSN	09320113
Journal	Parasitology Research
Volume Number	89
Issue Number	3
e-ISSN	14321955
Language	English
Publisher	Springer-Verlag
Publisher Date	2002-10-17
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Veterinary Parasitology Insect Science

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