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Infection and Immunity, May 2000, p. 2449-2456, Vol. 68, No. 5
Department of Immunology and Medical
Zoology1 and Laboratory of Host
Defenses, Institute for Advanced Medical
Sciences,2 Hyogo College of Medicine,
Nishinomiya, Hyogo 663-8501, Department of Host Defenses,
Research Institute for Microbial Diseases, Osaka University, Suita,
Osaka 565-0871,4 Laboratory Animal
Research Center, Institute of Medical Science, University of Tokyo,
Tokyo 108-8639,5 and Core Research for
Evolutional Science and Technology, Japan Science and Technology
Corporation, Tokyo,3 Japan
Received 3 November 1999/Returned for modification 5 December
1999/Accepted 26 January 2000
Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an
important role in natural killer cell activation and the T helper 1 (Th1) cell response, particularly in collaboration with IL-12. Since
Th1 cells play a pivotal role in the host defense against infection
with intracellular microbes, such as Leishmania major, we
investigated whether IL-18 is critically involved in protection against
L. major infection by activation of Th1 cells. We
administered IL-12 and/or IL-18 daily to L. major-susceptible BALB/c mice. Neither IL-12 (10 ng/mouse)
nor IL-18 (1,000 ng/mouse) induced wound healing, while daily injection
of IL-12 and IL-18 during the first week after infection strongly
protected the mice from footpad swelling by induction and activation of
Th1 cells. Furthermore, these mice acquired protective immunity. We
also investigated a protective role of endogenous IL-18 by using
anti-IL-18 antibody-treated C3H/HeN mice (an L. major-resistant strain) or IL-18 deficient
(IL-18
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Potentiality of Interleukin-18 as a Useful Reagent for Treatment
and Prevention of Leishmania major Infection
/
) mice with a resistant background (C57BL/6). We
found that in the absence of endogenous IL-18, these mice showed
prolonged footpad swelling as well as diminished nitric oxide
production. However, daily injection of IL-18 into
IL-18
/
mice corrected their deficiencies, suggesting
that these mice have Th1 cells that produce gamma interferon (IFN-
)
in response to IL-18. Indeed, these mice had normal levels of Th1
cells. Thus, IL-18 is not responsible for inducing Th1 cells but
participates in host resistance by its action in stimulating Th1 cells
to produce IFN-
. Our results also indicate the high potentiality of
IL-18 as a useful reagent for treatment as well as prevention against reinfection.
*
Corresponding author. Mailing address: Department of
Immunology and Medical Zoology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan. Phone:
81-(798) 45-6573. Fax: 81-(798) 40-5423. E-mail:
nakaken{at}hyo-med.ac.jp.
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