Preliminary results demonstrate that a specific blocker of CCR5 and CCR1 chemokine receptors, called met-RANTES, was able to decrease the experimental PD severity. However the mechanisms involved in such modulation, the ideal dose of met- RANTES to achieve the maximum remission of experimental PD, as well potential side effects concerning the infectious aspects of the disease remain unknown. Therefore, we initially performed a dose-response analysis of experimental PD outcome following met-RANTES therapy. The alveolar bone loss and inflammatory cell influx were used as the disease severity parameters, and the bacterial load in the periodontal tissues was used to monitor the control of infection. Except for the 0.05 mg dose, all the other doses resulted in a significant decrease of experimental PD severity. Interestingly, as a general rule a dose-response effect was identified in the attenuation of inflammatory cells influx, while a Kinase Inhibitor Library similar inhibition of bone resorption was achieved with the doses ranging from 0.5 up to 5 mg. The effectiveness of the met-RANTES in the control of inflammation-associated tissue damage is in agreement with previous studies , but deeper TWS119 comparisons with other models are impaired by the relatively low number of previous studies, performed in quite different experimental models usually investigating one or at most two different met-RANTES doses within a narrow interval. Interestingly, the PD treatment with 5 mg of met-RANTES dose impaired the control of periodontal infection, evidencing to distinct situations, where similar protective effects from the tissue destruction viewpoint are associated with distinct infectious outcomes. Therefore, in order to investigate the mechanisms underlying such differential response, the experimental groups receiving met-RANTES doses of 0.5 and 5 mg were selected for the further analysis. The first scenario, represented by the 0.5 mg met-RANTES protocol, can be interpreted as a clinically desired situation, where the tissue damage was minimized without interfering with host defense process. In fact, the 0.5 mg met-RANTES dose was effective in reducing F4/80 and CD3 cells , which present CCR1 and CCR5 receptor in its membranes, and also was observed a reduction in the tissue levels of pro-inflammatory cytokines IL-1b, TNF-a and IL-6. These cytokines are classically implicated in the onset and progression of PD by its role in osteoclastogenic process , being the reduction in its levels compatible with the attenuation of the experimental disease severity observed. Accordingly, met- RANTES therapy target cells from the monocytic lineage, characteristic sources of IL-1b, TNF-a and IL-6.