Pain/Functional Limitation Relationship in Patients With Knee Oa: The Influence of Aging

Abstract

Glucocorticoids (GC) are hormones with anti-inflammatory actions. Their actions are mediated by the glucocorticoid receptor (GCR)␣. 〈 GCR isoform called ␤ with dominant negative effect has been described. The GCR␤ is overexpressed in response to proinflammatory cytokines and in chronic inflammatory diseases like rheumatoid arthritis. The GCR␤ overexpression could induced a GC resistant state, favoring the development of autoimmune diseases. A relationship between infectious diseases and autoimmune diseases has been frequently proposed but it is still a matter of controversy. We proposed that a glucocorticoid resistance is induced in infectious diseases, which may lead in the appropriate background to the development or relapse of autoimmune diseases. Therefore, we evaluate if LPS can modulate the expression of GCR isotypes in vitro inducing the expression of the inhibitory GCR␤ and/or decreasing the expression of the active GCR␣. Methods: GCR ␣ and ␤ expression were evaluated by Western Blotting in monocytic cells (K562) cultured in presence of LPS (0, 10 pg/ml, 10 ng/ml, 10 g/ml) for 6 and 18 hours. Statistical analysis: Wilcoxon test. Results: After 6 hours of culture in presence of LPS at all concentrations tested, there was a significant decreased expression of both GCR isoforms. After 18 hours of culture a greater decreased in GCR␣ expression was observed while the expression of the GCR␤ was higher than the control. Conclusion: LPS in vitro modulates the expression of GCR isoforms which could lead to a glucocorticoid resistant state. This action could be a novel link between infections and autoimmune diseases.FONDECYT #103/0442. Abstract: The presence of anti-Ro/SSA antibody and its subtypes, Ro 52 kDa and Ro 60 kDa, has been associated with the clinical features in patients with systemic lupus erythematosus (SLE) and SjögrenЈs syndrome (SS), although there are many contradictory reports about it. Objective: To establish the association between total anti-Ro/SSA, Ro/ SSA 52 kDa and Ro/SSA 60 kDa, and clinical features in patients with LES and SS. Methods: Anti-Ro/SSA antibodies were determined in sera from 59 patients with diagnosed SLE (according to the ACR classification criteria, 1999), and 34 patients with diagnosed primary SS (pSS) and SS secondary (sSS) to other collagenopathies that are not SLE (according to the American-European Consensus Group classification criteria, 2002), by 2 ELISA methods. A commercial ELISA (#1), where total anti-Ro/SSA antibodies are detected, and ELISA (#2), which uses recombinant proteins to detect anti-Ro/SSA 52 and 60 kDa. The following clinical features were analyzed in the 93 patients: xerostomia, xerophthalmia, arthralgia, arthritis, photosensitivity, malar rash, central nervous system compromise and hematological compromise. Results: From 166 evaluated patients, 93 met the inclusion criteria, these were diagnosed: 59 as SLE and 34 as pSS or sSS. From the 59 SLE patients, 30 were anti-Ro/SSA negative and 29 positive, among the last group 18 were double positive (Ro 5...