Inhibition of intracellular proliferation of Leishmania parasites in vitro and suppression of skin lesion development in BALB/c mice by a novel lipid A analog (ONO-4007).

Mohammed A K Khan Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Motoyoshi Maruno Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Noor M Khaskhely Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Saeef T Ramzi Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Atsushi Hosokawa Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Hiroshi Uezato Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Eduardo A Gomez Landires Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Yoshihisa Hashiguchi Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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Shigeo Nonaka Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k998761@med.u-ryuku.ac.jp

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DOI:
https://doi.org/10.4269/ajtmh.2002.67.184
Volume/Issue:
Volume 67: Issue 2
Page(s):
184–190
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A synthetic lipid A analog (ONO-4007) exhibits antileishmanial activity by activating Leishmania-infected macrophages in experimental leishmaniasis. In the present in vitro study, ONO-4007 at concentrations between 0.01 and 1.00 mg/mL markedly inhibited the proliferation of Leishmania major and L. amazonensis promastigotes. Ultrastructurally, L. major-infected macrophages showed degenerated intracellular amastigotes after exposure to ONO-4007. Leishmania-infected macrophages treated with ONO-4007 showed poorly developed parasitophorous vacuoles. High levels of tumor necrosis factor-alpha were induced by ONO-4007 in Leishmania-infected macrophages. In this in vivo study, L. amazonensis-infected BALB/c mice were treated with a dose of 30 mg/kg of ONO-4007 by perilesional and peritoneal injections. The skin lesion size was assessed before treatment with ONO-4007 and at eight weeks after injection. The lesion size was significantly suppressed in mice perilesionally injected with ONO-4007 (P < 0.01) compared with the controls. The data from our present in vitro and in vivo studies indicate that ONO-4007 has an antileishmanial effect.

Author Notes

Published Online:
Aug 2002
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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