In Leishmania major-induced inflammation, interleukin-13 reduces hyperalgesia, down-regulates IL-1β 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-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.