Targeting Interleukin-18 (IL-18) in malaria infection

The potential of IL-18 as drug target during malaria infection was investigated in an experimental model. IL-18 production during the infection was modulated with IL-18 related drugs and the effects on the course of infection and the release of pro- and anti-inflammatory cytokines were evaluated. Ma...

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Main Authors: Basir, Rusliza, Kartini, Hasballah, Ismail, Sabariah, Gam, Lay Harn, Mahmud, Roziahanim, Abdul Majid, Amin Malik
Format: Conference or Workshop Item
Language:English
Published: 2009
Subjects:
Online Access:http://psasir.upm.edu.my/id/eprint/12217/1/ID%2012217.doc
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author Basir, Rusliza
Kartini, Hasballah
Ismail, Sabariah
Gam, Lay Harn
Mahmud, Roziahanim
Abdul Majid, Amin Malik
author_facet Basir, Rusliza
Kartini, Hasballah
Ismail, Sabariah
Gam, Lay Harn
Mahmud, Roziahanim
Abdul Majid, Amin Malik
author_sort Basir, Rusliza
collection UPM
description The potential of IL-18 as drug target during malaria infection was investigated in an experimental model. IL-18 production during the infection was modulated with IL-18 related drugs and the effects on the course of infection and the release of pro- and anti-inflammatory cytokines were evaluated. Malaria infection was initiated by inoculation of mice with Plasmodium berghei parasite. Modulation of IL-18 production was carried out by treatment with recombinant mouse IL-18 binding protein, anti-IL-18 monoclonal antibody or recombinant IL-18. The plasma concentrations of IL-18 and other cytokines were measured by ELISA technique. IL-18 expression in local tissues was determined through western blotting method. The course of infection was monitored throughout the infection and treatment. Plasma IL-18 was significantly elevated and positively correlated with parasitaemia development during the infection. Significant expressions of IL-18 were observed in the spleen, liver and brain tissues of infected mice. Plasma concentrations of pro-inflammatory cytokines (TNF, IL-1, IFN, IL-6) decreased significantly upon inhibition and neutralization of IL-18, whereas the anti-inflammatory cytokine IL-10 increased significantly. Augmenting the production of IL-18 during the infection significantly increased the release of pro-inflammatory cytokines further in the plasma whereas the anti-inflammatory cytokine was reduced. Significant increase in parasitaemia development and earlier mortality were also observed in infected mice when IL-18 release was further augmented. Results suggest the crucial role of IL-18 in malaria infection and targeting IL-18 may prove to be beneficial to the host and IL-18 may potentially be developed as an important immunotherapeutic target for malaria therapy.
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spelling upm.eprints-122172015-01-05T04:30:59Z http://psasir.upm.edu.my/id/eprint/12217/ Targeting Interleukin-18 (IL-18) in malaria infection Basir, Rusliza Kartini, Hasballah Ismail, Sabariah Gam, Lay Harn Mahmud, Roziahanim Abdul Majid, Amin Malik The potential of IL-18 as drug target during malaria infection was investigated in an experimental model. IL-18 production during the infection was modulated with IL-18 related drugs and the effects on the course of infection and the release of pro- and anti-inflammatory cytokines were evaluated. Malaria infection was initiated by inoculation of mice with Plasmodium berghei parasite. Modulation of IL-18 production was carried out by treatment with recombinant mouse IL-18 binding protein, anti-IL-18 monoclonal antibody or recombinant IL-18. The plasma concentrations of IL-18 and other cytokines were measured by ELISA technique. IL-18 expression in local tissues was determined through western blotting method. The course of infection was monitored throughout the infection and treatment. Plasma IL-18 was significantly elevated and positively correlated with parasitaemia development during the infection. Significant expressions of IL-18 were observed in the spleen, liver and brain tissues of infected mice. Plasma concentrations of pro-inflammatory cytokines (TNF, IL-1, IFN, IL-6) decreased significantly upon inhibition and neutralization of IL-18, whereas the anti-inflammatory cytokine IL-10 increased significantly. Augmenting the production of IL-18 during the infection significantly increased the release of pro-inflammatory cytokines further in the plasma whereas the anti-inflammatory cytokine was reduced. Significant increase in parasitaemia development and earlier mortality were also observed in infected mice when IL-18 release was further augmented. Results suggest the crucial role of IL-18 in malaria infection and targeting IL-18 may prove to be beneficial to the host and IL-18 may potentially be developed as an important immunotherapeutic target for malaria therapy. 2009 Conference or Workshop Item NonPeerReviewed application/msword en http://psasir.upm.edu.my/id/eprint/12217/1/ID%2012217.doc Basir, Rusliza and Kartini, Hasballah and Ismail, Sabariah and Gam, Lay Harn and Mahmud, Roziahanim and Abdul Majid, Amin Malik (2009) Targeting Interleukin-18 (IL-18) in malaria infection. In: 6th European Congress on Tropical Medicine and International Health, 6-10 Sep. 2009, Verona, Italy. . Interleukins Malariotherapy Infection
spellingShingle Interleukins
Malariotherapy
Infection
Basir, Rusliza
Kartini, Hasballah
Ismail, Sabariah
Gam, Lay Harn
Mahmud, Roziahanim
Abdul Majid, Amin Malik
Targeting Interleukin-18 (IL-18) in malaria infection
title Targeting Interleukin-18 (IL-18) in malaria infection
title_full Targeting Interleukin-18 (IL-18) in malaria infection
title_fullStr Targeting Interleukin-18 (IL-18) in malaria infection
title_full_unstemmed Targeting Interleukin-18 (IL-18) in malaria infection
title_short Targeting Interleukin-18 (IL-18) in malaria infection
title_sort targeting interleukin 18 il 18 in malaria infection
topic Interleukins
Malariotherapy
Infection
url http://psasir.upm.edu.my/id/eprint/12217/1/ID%2012217.doc
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AT gamlayharn targetinginterleukin18il18inmalariainfection
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