MPO and IgG are products of neutrophils and B cells respectively, cells types supposedly to not be primarily affect by the interference with CCR1 and CCR5 EX 527 promoted by met-RANTES. In accordance with such hypothesis, 5 mg dose of met- RANTES treatment reduced the number of both Gr1+ and CD19+ cells in the infected periodontal tissues. In addition, it is important to mention that the expression of the antimicrobial enzyme iNOS was also greatly diminished by the 5 mg met- RANTES dose. Taken together, the reduction in the innate and adaptive antimicrobial LDN-193189 in vivo response is possible responsible for the increase in the bacterial load found in periodontal tissues. Accordingly, MPO, iNOS and IgG are supposed to contribute to the killing of periodontal bacteria. Therefore, it is possible to conclude that an excessive downregulation of host response by the high met-RANTES doses significantly impair host response overcoming the protective effect presented by lower doses. In fact, the significant increase in serum CRP levels reinforces the compromised host response presented by mice treated with high met-RANTES doses. In this setting, an important question refers to nature and intensity of host response required to assure a proper defense against the periodontopathogens. Since a series of therapeutic proposals targets the modulation of host response, the exact determination of the leukocyte subsets, cytokines and antimicrobial factors really involved in the control of periodontal infection is fundamental to direct future host-targeted therapies. When the results presented here are compared with a previous study of our group, were a mice strain selected for minimal inflammatory response was evaluated , interesting information arise. AIRmin strain and the C57BL/6 mice treated with 5 mg met-RANTES dose present similar inflammatory and bone loss scores, and also similar production of IL-1b and TNF-a. However, AIRmin strain efficiently controls the experimental periodontal infection, a finding associated with higher IFN-c production than met-RANTES-treated mice. Also, while MPO and iNOS levels were similar in AIRmin strain and met- RANTES-treated mice, 5 mg met-RANTES treatment resulted in lower IgG response than observed in AIRmin strain. In accordance with previous studies , these results point to important roles of IFN-c and antibody production in the control of periodontal infection. Therefore, it is possible to suggest that immunoregulatory strategies aimed to control PD should not interfere with these mediators.