Effect of ß-blockers on Leishmania major induced hyperalgesia and the levels of IL-1ß, TNF-α and KC

Abstract

Infection with a high dose of L.majorleads to parasite dissemination and exacerbation of the disease in susceptible BALB/c mice with persistent hyperalgesia. According to the literature, this hyperalgesia is accompanied by an up-regulation of some pro-inflammatory cytokines though it is IL-1Beta and IL-6 independent. On the other hand, cyclooxygenase-inhibitors and Beta-blockers are known to limit hyperalgesia in several models other than cutaneous leishmaniasis. In this study, we investigated the effect of daily treatment with indomethacin and atenolol on the L. majorinduced hyperalgesia in BALB/c mice. In this study, 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 TNF-alpha. We also demonstrate that indomethacin was not efficient in reducing hyperalgesia in high dose L.major model, whereas, atenolol are able to attenuate it. We have shown here that neither IL-1Beta nor KC have a direct role in the observed hyperalgesia, and that TNF- alpha seems to play this role since its level was reduced during the period of atenolol treatmemt which correlates well with the reduction of hyperalgesia.