Abstract
Immunomodulatory therapy of inflammatory rheumatic diseases, especially in refractory forms of systemic lupus erythematosus (Rovensky et al.) and rheumatoid arthritis (Mateicka et al.) has its tradition. The very immunosuppressive therapy may induce the development of resistance and to participate in recurrent secondary infections in patients suffering from systemic diseases of the connective tissue. Alternatives of immunomodulatory therapy are therefore sough for that would eliminate some adverse effects of immunosuppressive agents on the cell-mediated and non-specific immunity function, and would favorably affect the clinical condition of the patient. To verify our working hypothesis concerning the appropriateness of immunomodulatory therapy with Ribomunyl®, the adjuvant arthritis model in rats was chosen. Following drugs and their combinations were orally administered to animals in a long-term prophylactic course: Cyclosporine A (CyA, 2,5 mg/kg/day), methotrexate (MTX, 0,3 mg/kg, 2 times a week), Ribomunyl® (25 mg/kg 4 times a week), CyA+MTX, CyA+Ribomunyl®, MTX+Ribomunyl®, and the three-combination of CyA+MTX+ Ribomunyl®. When given in combination, both the doses and the frequency of administration were the same as when the drugs were administered alone. The following markers of inflammation and arthritic process were measured: serum albumin, joint X-ray, hind paw swelling, and on day 40 of the study, bone mineral density (BMD) and bone mineral content (BMC). Our results showed that Ribomunyl® alone has no marked effect on markers of inflammation and arthritis in animals with adjuvant arthritis. When combined with the immunosuppressive drugs CyA and MTX, a similar and/or better therapeutical effect was observed than with the basic drug without Ribomunyl®. However, the effect of the three-combination of CyA+MTX+Ribomunyl® was rather remarkable. This combination had the most pronounced therapeutical effect on rats with adjuvant arthritis. It significantly inhibited inflammatory and arthritic markers as well as BMD and BMC reductions. Our results obtained using the adjuvant arthritis model suggest that immunomodulatory procedures are promising. These result therefore need to be verified in additional animal models and markers of cell-mediated immunity and/or cytokines involved in the induction of this therapeutic effect should be investigated.
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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