The effect of IL-10 and IL-13 on Leishmania major induced inflammation as to hyperalgesia and the levels of IL-1B, IL-6, and IL-4

Abstract

Infection with the protozoan parasite Leishmania major in murine models causes either a local, healing cutaneous lesion or a fatal, disseminated disease depending on the strain of the mouse. The observed outcome is based on the development of a T helper 1 (Th1) response in the resistant mice or a T helper 2 (Th2) response in the susceptible mice. According to the literature, upon injection with high doses of Leishmania major in the hind paw of susceptible mice leads to obvious hyperalgesia even before the appearance of the lesion (which is accompanied by the up-regulation of some pro-inflammatory cytokines such as IL-1Beta 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 high dose of L. major causes a state of hyperalgesia during early infection accompanied by an up-regulation of IL-1Beta and a short burst of IL-6. This low pain threshold and the high level of IL-1Beta are reversed within two weeks of infection. We also demonstrate that IL-10 and IL-13 are able to reduce this evoked hyperalgesia in high dose models. We have shown here that neither IL-1Beta nor IL-6 have a direct role in this hyperalgesia. Moreover, since IL-1Beta remains low even when IL-13 is not injected, this means that it is inducing IL-4 or its own (IL-13) production. However, in this study we assessed IL-4 levels and it is shown not to be upregulated this leads to the possibility that IL-13 is upregulating itself.