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The Role of Cytokines in the Regulation of Hyperalgesia and Disease Progression in Leishmania major Infection.

Karam, Marc Christophe. (2005) The Role of Cytokines in the Regulation of Hyperalgesia and Disease Progression in Leishmania major Infection. Doctoral thesis, University of Surrey (United Kingdom)..

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Murine models of infection with the protozoan parasite Leishmania major cause either a local, healing cutaneous lesion or a fatal, disseminated disease depending on the strain of the mouse. This is due to the preferential development of T helper 1 (Th1) response in the resistant mice and of T helper 2 (Th2) response in the susceptible mice. It has been shown, however, that upon injection with a low dose of the parasite, susceptible mice are capable of developing protective immunity by favouring a Th1 response. Moreover, the subcutaneous injection of high doses of Leishmania major in the hind paw of susceptible mice leads to an obvious hyperalgesia even before the appearance of the lesion (which is accompanied by the up-regulation of some pro-inflammatory cytokines such as IL-1β and IL-6). On the other hand, IL-10 and IL-13, produced mainly by Th2 cells, have been shown to have hypoalgesic effects in other models. This thesis investigates the effect of IL-10 and IL-13 on the L. major-induced inflammation in mice with respect to hyperalgesia and course and outcome of infection. We demonstrate that the injection of susceptible mice (BALB/c mice) with a low dose of L. major causes a state of hyperalgesia during early infection accompanied by an up-regulation of IL-1β and a short burst of IL-6. This low pain threshold and the high level of IL-1β are reversed within two weeks of infection. We also demonstrate that IL-10 and IL-13 are able to reduce this evoked hyperalgesia in both, the high and the low dose models. However, the early presence of the hypoalgesic doses of those two cytokines leads to a prolonged hyperalgesia and inhibits the suspected Th2/Thl switch in the low dose model.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Karam, Marc Christophe.
Date : 2005
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2005.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 11:56
Last Modified : 06 May 2020 12:02

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