Association between rheumatoid arthritis and periodontal disease: evaluation of the IL-23/IL-17 axis

Abstract

Inflammatory-immune host responses have an important role on homeostasis maintenance, as well as in the beginning and progression of many autoimmune, inflammatory and infectious diseases. Periodontal disease (PD) and rheumatoid arthritis (RA) share many pathological characteristics including changes in the pattern and levels of cytokines and their antagonists. Also, this immune-inflammatory imbalance has been considered responsible for most of tissues destruction observed during the progression of these diseases. A higher PD prevalence has been observed in RA patients, as well as a decreasing of RA severity after infection control with periodontal treatment. Some parameters as RA duration and severity degree, oral hygiene control, gingival inflammation and drugs used for RA patients are discussed as influence factors in PD and RA relationship which still remains controversial. Pro-inflammatory cytokines have a fundamental role in the pathogenesis of both disorders. In this context, recent evidences have suggested a relevant role of the inflammatory axis IL-23/IL-17 in RA pathogenesis through concurrency and/or synergism with other cytokines such as IL-1beta and TNF-alpha, with a subsequent amplification of inflammation and changes in the RANK-RANKL/OPG axis (osteoclastogenesis). The role of Th17 and of IL-23/IL-17 axis in the PD immunopathology is still unknown and poorly investigated. However, a pro-inflammatory activity of IL-17 in the PD pathogenesis as observed for RA has been suggested by papers where higher levels of IL17 were detected in PD sites. In recent literature, studies of PD models for IL-23/IL-17 axis investigation were not found, neither the simultaneous induction of RA and PD with the aim to investigate the relationship between these chronic/inflammatory diseases. Thus, this project has the specific aims: -evaluate the association between PD and RA in experimentally-induced PD and RA by, respectively, bacterial LPS and mBSA, in mice. -evaluate the expression of IL-23 and IL-17 and their role in the physiopathology of PD associated or not to RA in experimentally-induced PD and RA by, respectively, bacterial LPS and mBSA, in IL-17 receptor knock-out mice. (AU)