In Leishmania major-induced inflammation, interleukin-13 reduces hyperalgesia, down-regulates IL-1ß and up-regulates IL-6 in an IL-4 independent mechanism.

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-1ß 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-1ß 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-1ß, 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-1ß 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-1ß 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.

Interleukin-13 reduces hyperalgesia and the level of interleukin-1ß in BALB/c mice infected with Leishmania major with an up-regulation of interleukin-6.

The anti-inflammatory cytokines interleukin-10 (IL-10) and interleukin-13 (IL-13) were shown to reduce hyperalgesia in some models such as rats exposed to UV rays. In addition, IL-10 was also shown to reduce hyperalgesia in high dose of Leishmania major-induced inflammation in BALB/c mice accompanied by a significant decrease in the levels of interleukin-1ß (IL-1ß) in the paws of infected mice, while no effect on the levels of IL-6 was observed. In this study, we injected BALB/c mice with a high dose of L. major and treated them with IL-13 (15 ng/animal) for twelve days (excluding the weekends) and hyperalgesia was assessed using thermal pain tests. Furthermore, the levels of IL-1ß and IL-6 were also assessed at different post-infection days. Our results show that IL-6 and more importantly IL-1ß don't play a direct role in the L. major-induced hyperalgesia and that IL-13 induces this hyperalgesia through the down-regulation of IL-1ß and another proinflammatory cytokine (most probably TNF-α). Furthermore, our data show that IL-13 leads to the upregulation of the level IL-6 which initially seems to have no direct role in the induced hyperalgesia. Therefore, we suggest that the L. major-induced hyperalgesia is mainly mediated by the cytokine cascade leading to the production of sympathetic amines.