Preventive and therapeutic anti-TNF-α therapy with pentoxifylline decreases arthritis and the associated periodontal co-morbidity in mice

Aims: The association between rheumatoid arthritis (RA) and periodontal disease (PD) has long been studied and some reports suggest that treating RA may improve the associated PD, and vice versa. This study aimed to evaluate the effects of an anti-tumor necrosis factor (TNF)-alpha therapy with pentoxifylline (PTX) in an experimental model of RA-associated PD. Main methods: Male C57BL/6 mice were subjected to chronic antigen-induced arthritis (AIA) and daily treated with PTX (50 mg/kg, i.p.) using preventive (Pre-PTX) or therapeutic (The-PTX) strategies. Fourteen days after the antigen challenge, mice were euthanized and knee joints, maxillae and serum were collected for microscopic and/or immunoenzymatic analysis. Key findings: AIA triggered significant leukocyte recruitment to the synovial cavity, tissue damage and proteoglycan loss in the knee joint. Pre-PTX and The-PTX regimens decreased these signs of joint inflammation. The increased levels of TNF-alpha and IL-17 in periarticular tissues of AIA mice were also reduced by both PTX treatments. Serum levels of C-reactive protein, which were augmented after AIA, were reduced by the PTX regimens. Concomitantly to AIA, mice presented alveolar bone loss, and recruitment of osteoclasts and neutrophils to periodontal tissues. Pre-PIX and The-PTX prevented and treated these signs of PD. PTX treatment also decreased TNF-alpha and increased IL-10 expression in the maxillae of AIA mice, although it did not affect the expression of IFN-gamma and IL-17. Significance: The current study shows the anti-inflammatory and bone protective effects of preventive and therapeutic PTX treatments, which decreased the joint damage triggered by ALA and the associated periodontal co-morbidity. (C) 2013 Elsevier Inc. All rights reserved,