PMID- 10768930
OWN - NLM
STAT- MEDLINE
DCOM- 20000613
LR  - 20210526
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 68
IP  - 5
DP  - 2000 May
TI  - Potentiality of interleukin-18 as a useful reagent for treatment and prevention 
      of Leishmania major infection.
PG  - 2449-56
AB  - 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(-/-)) 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-gamma) 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-gamma. Our results also indicate the high potentiality of IL-18 as a useful 
      reagent for treatment as well as prevention against reinfection.
FAU - Ohkusu, K
AU  - Ohkusu K
AD  - Department of Immunology and Medical Zoology, Hyogo College of Medicine, 
      Nishinomiya, Hyogo 663-8501, Japan.
FAU - Yoshimoto, T
AU  - Yoshimoto T
FAU - Takeda, K
AU  - Takeda K
FAU - Ogura, T
AU  - Ogura T
FAU - Kashiwamura, S
AU  - Kashiwamura S
FAU - Iwakura, Y
AU  - Iwakura Y
FAU - Akira, S
AU  - Akira S
FAU - Okamura, H
AU  - Okamura H
FAU - Nakanishi, K
AU  - Nakanishi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Interferon-gamma/genetics/immunology
MH  - Interleukin-12/administration & dosage/immunology
MH  - Interleukin-18/administration & dosage/genetics/*immunology
MH  - Leishmania major/*immunology
MH  - Leishmaniasis, Cutaneous/*immunology/pathology/prevention & control
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
PMC - PMC97445
EDAT- 2000/04/18 09:00
MHDA- 2000/06/17 09:00
PMCR- 2000/05/01
CRDT- 2000/04/18 09:00
PHST- 2000/04/18 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/04/18 09:00 [entrez]
PHST- 2000/05/01 00:00 [pmc-release]
AID - 1619 [pii]
AID - 10.1128/IAI.68.5.2449-2456.2000 [doi]
PST - ppublish
SO  - Infect Immun. 2000 May;68(5):2449-56. doi: 10.1128/IAI.68.5.2449-2456.2000.