Abstract
Adjuvant-induced arthritis (AIA) in rats is a relevant model for human rheumatoid arthritis (RA). In this study, th expression of the cytokines TNF-alpha, IL-1 and IL-6, as well as the chemokines MIP-1-alpha, MCP-1 and ENA-78 in the sera and joint homogenates of AIA and control, sham-injected rats was studied over a 47-day period. All of these cytokines and chemokines showed increased production in AIA. In addition, TNF-alpha, IL-1, ENA-78 and MIP-1-alpha could be termed as mediators, as their production increased in the first 14-21 days and it correlated with early events in synovitis, such as neutrophil ingress, joint swelling and general symptoms. TNF-alpha may have mostly systemic, while IL-1 mainly local synovial effects. IL-6 and MCP-1 were found to be late inflammatory mediators, as their secretion was up-regulated after 2 weeks post-adjuvant injection and remained high during the observation period. Also, significant correlation was found between the production of TNF-alpha and that of chemokines. In conclusion, the differential expression of and late cytokines and chemokines may account for various events underlying synovitis in AIA.
Highlights
The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for rheumatoid arthritis (RA)
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA)
Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, this did not reach statistical significance (P = 0,18)
Summary
The presence of autoantibodies directed to citrullinated antigens in serum is highly specific for RA. Anti-CCP concentrations (expressed in Units per mg total IgG) were on average 1.34 times higher in SF compared to serum (n = 20, P < 0.05) or 1.37 when only positive samples were included (n = 11, P < 0.05) Conclusion: Citrullinated antigens are present in the synovia of both RA and control patients with similar prevalence. At higher concentrations (>1ng/μl) of RNA-oligonucleotides unspecific hybridization-signals prevailed in tissues of all diseases (even in normal controls) The combination of both methods (in situ-hybridization and immunohistochemistry) identifies the single cells inside the synovial lining layer which contains the highly expressed RAB3 “Kreisler” (maf B) gene. Conclusions: These data demonstrates for the first time that statins (and fluvastatin) are able to inhibit an endothelial proadhesive and pro-inflammatory phenotype induced by different stimuli including anti-β2GPI antibodies or pro-inflammatory cytokines These findings suggest a potential usefulness for statins in the prevention of the APS pro-atherothrombotic state
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