Antigen-induced inflammatory mechanical hypernociception in mice is mediated by IL-18

Verri Jr, W. A., Cunha, T. M., Parada, C. A., Poole, S., Liew, F. Y., Ferreira, S. H. and Cunha, F. Q. (2007) Antigen-induced inflammatory mechanical hypernociception in mice is mediated by IL-18. Brain, Behavior, and Immunity, 21(5), pp. 535-543. (doi: 10.1016/j.bbi.2006.11.005)

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Publisher's URL: http://dx.doi.org/10.1016/j.bbi.2006.11.005

Abstract

There is pre-clinical evidence that therapies targeting IL-18 might be beneficial in controlling arthropathies, which are accompanied by hypernociception (nociceptor sensitization). In the present study, we addressed the hypernociceptive role of IL-18 in a model of antigen-induced inflammation in mice and its mechanisms. In naïve mice, the intraplantar injection of IL-18 induced dose- and time-dependent mechanical hypernociception, which was inhibited in IFN-γ deficient (−/−) mice, and by the pre-treatment with bosentan (dual endothelin [ET] receptor antagonist), BQ123 (ETA receptor antagonist) or indomethacin (cyclooxygenase inhibitor). IL-18 hypernociception was unaffected in TNFR1−/− mice or by the pre-treatment with sIL-15Rα (soluble form of IL-15 receptor), BQ788 (ETB receptor antagonist) or guanethidine (sympathetic blocker). The ovalbumin (OVA) challenge-induced mechanical hypernociception in immunized mice was inhibited by the pre-treatment with anti-IL-18 antibody or in IL-18−/− mice. Furthermore, IL-18 induced significant IFN-γ production in the paw skin of naïve mice. The OVA challenge-induced IFN-γ and ET-1 productions were inhibited in IL-18−/− immunized mice, as well as ET-1 production in IFN-γ−/−immunized mice. In addition, significant PGE2 production was detected after IL-18 or ET-1 (via ETAreceptors) injection in naïve mice. Taken together with previous data, these results suggest that IL-18 plays a significant role in antigen-induced inflammatory hypernociception via the production of IFN-γ, ET-1 and PGE2. Thus, IL-18 and IL-18-downstream mediators demonstrated herein might constitute targets to inhibit antigen-induced inflammatory pain.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo
Authors: Verri Jr, W. A., Cunha, T. M., Parada, C. A., Poole, S., Liew, F. Y., Ferreira, S. H., and Cunha, F. Q.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Brain, Behavior, and Immunity
ISSN:0889-1591
ISSN (Online):1090-2139
Published Online:27 December 2006
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
380241Toll-like receptors on T cellsFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine