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Rheumatoid arthritis (RA) is associated with an excess cardiovascular morbidity and mortality, related to systemic inflammation with endothelial dysfunction (ED) and impaired flow-mediated vasodilation (FMD). We assessed the FMD response to anti-TNF-alpha treatments in 28 RA patients, aged 49.8+/-15.3 years: an unpaired FMD was found in 66.7 percent of our cases and was restored after 6 weeks of anti-TNF-á treatment (13.5+/-5.3 percent vs 4.6+/-4.1 percent, p less than 0.05). Twenty-five percent of the infliximab patients demonstrated a long term response, compared with 60 percent of etanercept and 100 percent of adalimumab patients, after 2 years (p less than 0.01). Infections (3 cases), myocardial ischemia (1 case) or loss of response (4 cases) were associated with a worsened FMD, restored by shifting to adalimumab. The present study confirms that ED is an RA systemic disease marker, responsive to anti-TNF-alpha treatment and sensitive to clinical events or to a loss of response, underlying the biological coherence between synovial and endothelial inflammation.

Palladium (Pd) and its compounds can cause sensitization, asthma and skin disorders. Sensitization to Pd is increasing in the European general population. In this study, Wistar rats were exposed for two weeks to 0, 1, 10,100 and 250 ng ml-1 of Pd as potassium hexachloro-palladate in drinking water. At the end of exposure, possible changes in two type-1 cytokines (IL-2, INF-gamma) and one type-2 cytokine (IL-4) in the serum were measured. Our findings suggest that, after a sub-acute exposure, a moderate level of Pd causes a strong Th2 response. This also occurs at higher concentrations. Although no effect on Th1 cells is observed up to a concentration of 250 ng/ml, a significant increase in IL-2 production is reported thereafter. These results therefore suggest that in sub-acute exposure, Pd exerts a significant immuno-modulating effect, altering the Th1/Th2 cytokine balance, even at low exposure doses. Our preliminary results indicate the need to carry out further studies to observe the effect of different types of Pd compounds and to measure other types of cytokines both in the animal model used in our study and in other models.