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Cutaneous leishmaniasis is a major global health issue, affecting more than 88 countries with 0.7-1.2 million new cases per year. T helper polarization plays a significant role in disease outcome, with Th1 responses being associated with resistance and Th2 responses being associated with susceptibility. IL-13 is an important Th2 cytokine with structural and functional similarities to IL-4. In this study, we demonstrate that administering exogenous IL-13 to Leishmania major-infected BALB/c mice increases parasite load in the infected paw and decreases tissue levels of the key Th1/Th2 cytokines IFN-γ and IL-4, respectively. Infecting BALB/c mice with a low dose of L. major has previously been shown to confer resistance to re-infection with a higher dose. In this study, we demonstrate that administration of exogenous IL-13 early in the course of the initial low-dose infection abrogates acquired resistance to high-dose re-infection, as measured by infected paw thickness., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Infection with high dose Leishmania major induces a sustained hyperalgesia in BALB/c mice while low dose induces a short lived hyperalgesia both accompanied with the upregulation of IL-1β and IL-6. Although IL-13 was shown to reduce the high dose L. major hyperalgesia during the treatment period, this effect was accompanied by a significant decrease in the levels of IL-1β and a significant increase in the levels of IL-6 in the paws of mice even beyond this period. Those results suggest that IL-13 exerts those effects via the induction of another mediator, IL-4 being a potential candidate due to its known hypoalgesic effects in other models and to its close functional closeness to IL-13 especially at the level of receptors. In this study we correlated the pain thresholds and the levels of IL-1β, IL-6 and IL-4 with the period of IL-13 treatment and beyond it in mice infected with high and low dose of L. major. The results of both models show that IL-1β plays no direct role in provoking the observed hyperalgesia after stopping the treatment with IL-13 which is in contrary to IL-6 which might be a key player after the treatment period. Furthermore we demonstrate that there is no correlation between the levels of IL-4, hyperalgesia, the decreased IL-1β levels and the increased levels of IL-6 in the paws of IL-13 treated and L. major (high and low dose) infected BALB/c mice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Interleukin-13 (IL-13) is a powerful anti-inflammatory cytokine that was previously shown to be a susceptibility factor for Leishmania major (L. major) infection. In this study we report a different role for IL-13 in rats infected with L. major; rIL-13 stimulates expression of pro-inflammatory cytokines and IL-12 which is a key cytokine in protective immunity against Leishmania. Infected rats received daily injections of rIL-13 for eight consecutive days which resulted in increased pain perception for the first week post-infection assessed by thermal pain tests. This hyperalgesia was accompanied by a sustained early up-regulation of interleukin-1beta followed by an up-regulation of IL-12p70. Real-time PCR showed no negative impact for rIL-13 upon the clearance of the parasites from the infection sites and blood.

Infection with a high dose of Leishmania major has been shown to induce hyperalgesia in BALB/c mice accompanied by a sustained upregulation of Interleukin-1beta (IL-1beta) and an early upregulation of Interleukin-6 (IL-6). On the other hand, Interleukin 10 (IL-10) has been demonstrated to be hypoalgesic in other models such as rats exposed to UV rays. In this study, we injected BALB/c mice with a high dose of Leishmania major and treated them with IL-10 (15 ng/animal) for six consecutive days. Hyperalgesia was assessed using thermal pain tests and the levels of IL-1beta and IL-6 were also assessed at different post-infection days. Our results show that IL-10 can reduce the Leishmania major-induced hyperalgesia during the treatment period through a direct effect on the levels of IL-1beta which seems to play an important role in this hyperalgesia induction since its level was reduced during the period of IL-10 injection and was increased again when this treatment was stopped. On the contrary IL-10 has no direct effect on the levels IL-6 which seems to have no direct role in the induced hyperalgesia.