RGD Reference Report - Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection. - Rat Genome Database

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Potentiality of interleukin-18 as a useful reagent for treatment and prevention of Leishmania major infection.

Authors: Ohkusu, K  Yoshimoto, T  Takeda, K  Ogura, T  Kashiwamura, S  Iwakura, Y  Akira, S  Okamura, H  Nakanishi, K 
Citation: Ohkusu K, etal., Infect Immun. 2000 May;68(5):2449-56.
RGD ID: 8655909
Pubmed: PMID:10768930   (View Abstract at PubMed)
PMCID: PMC97445   (View Article at PubMed Central)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL18Humanleishmaniasis treatmentISOIl18 (Mus musculus) RGD 
Il18Ratleishmaniasis treatmentISOIl18 (Mus musculus) RGD 
Il18Mouseleishmaniasis treatmentIDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)


Additional Information