1C). Similar results were observed in animals injected with Cdt venom 11 days after intraplantar injection of BCG. The edema was similar Rapamycin in both groups until the 11th day, when one of the groups received

the venom injection. In the following days, we observed a significant decrease in the volume of the paws of the animals injected with Cdt venom compared to that observed in control animals (Fig. 1D). Studying a possible mechanism involved in the inhibitory effect of the Cdt venom on this chronic inflammatory process, we observed that 6 h after injection with BCG, the groups treated with dexamethasone or Cdt venom and the group pre-treated with dexamethasone and subsequently injected with Cdt venom developed significantly less paw edema than the control group. However, when assessed 48 h after injection of BCG, the group injected with ALK inhibitor Cdt venom was the only group that showed significantly less intense edema (Fig. 2A). In another set of experiments, the group injected only with Cdt venom and the group pre-treated with indomethacin and later injected with Cdt venom developed significantly less paw edema than the control group 6 and 48 h after intraplantar

injection of BCG. At these times, the group treated only with indomethacin presented with edema similar to the control group (Fig. 2B). When zileuton was used to study its effect on the development of edema induced by BCG and on the inhibitory effect of Cdt venom, results showed that the group injected only with Cdt venom was unique in producing significantly less paw edema than the control group 6 and 48 h after intraplantar injection of BCG. The group treated with zileuton showed edema of a magnitude similar to that observed in the control group at both time periods studied. However, in the group that was pretreated with zileuton

and then subsequently received Cdt venom, edema was Chlormezanone similar to that observed in the control group in the 6th hour but was significantly higher than the edema observed in the control group 48 h after injection of BCG (Fig. 3A). Similar results were observed in groups treated with Boc2 before the injection of Cdt venom. Boc2 did not altered the edema induced by BCG, but blocked the inhibitory effect of the Cdt venom on the paw edema induced by BCG in both periods studied (Fig. 3B). To determine which toxin is responsible for the inhibitory effect observed in the crude Cdt venom, we used three fractions obtained from a MonoQ column. We can see that the group injected with the Cdt venom presents with edema that is significantly less than that of the control group (treated with saline). Of the three fractions used, only the group treated with the fraction II, corresponding to crotoxin, showed significantly less intense edema than that observed in the control group and similar to what occurred with the group treated with the crude venom.