However, Z-VAD-FMK concentration it is now recognized that the chronic stimulation of this systemic inflammatory response provides markers for risk of disease, as well as the probability that the biomolecules of this response can actually contribute to the disease processes. Numerous studies have reported that chronic periodontal infections trigger chronic inflammation that is expressed locally as periodontitis [12,13], and systemically by elevations in various inflammatory mediators [2]. The levels of these mediators are associated generally with the severity/extent of periodontal disease, frequently decrease significantly with periodontal therapy and are decreased

in patients who become edentate (Cunningham LL, Novak MJ, Stevens J, Abadi B and Ebersole JL. The oral-systemic link: a bidirectional relationship. submitted.). Thus, while the ‘cause and effect’ relationship between the systemic inflammatory mediators and periodontitis is difficult to document unequivocally, the breadth of evidence indicates that chronic periodontal infections may be a contributor to the burden of risk for initiating and/or sustaining symptoms associated with chronic inflammatory diseases. We have described a non-human primate model of a chronic polymicrobial periodontal infection and have demonstrated a Maraviroc pattern of host responses similar to those which occur in human disease

[53–55]. The baboon model of ligature-induced periodontitis and pregnancy can be used to assess the host response profiles during disease and to identify some biological links with adverse pregnancy outcomes [46]. Periodontitis in the non-human Clomifene primates elicited by ligature placement is accompanied by changes in the subgingival microbial ecology with bacterial species similar to those in human disease [47,56,57]. This

chronic oral infection elicits elevated levels of local inflammatory, innate and acquired immune mediators [12,13,58,59]. The results of this report focused upon the capacity of the oral infection and disease to trigger changes in the systemic host response apparatus, manifested by changes in various acute phase reactants, and inflammatory mediators and cytokines/chemokines. Our previous results have demonstrated extensive variability in periodontal clinical presentation of the group of female baboons, not dissimilar from the heterogeneity reported in human populations, with some animals showing pre-existing naturally occurring mild to moderate periodontitis [46]. Additionally, while all the experimental animals subjected to tooth ligation developed significant increases in gingival inflammation and destructive disease following placement of ligatures during pregnancy, the changes in disease in response to ligation exhibited individual variation.