TY - JOUR T1 - Effects of dexamethasone on lymphocyte proliferation and cytokine production in rheumatoid arthritis. JF - The Journal of Rheumatology JO - J Rheumatol SP - 46 LP - 51 VL - 29 IS - 1 AU - AntonioSergioR De AU - Heloisa M Blotta AU - Roney L Mamoni AU - Paulo Louzada AU - Manoel B Bertolo AU - Norma T Foss AU - Ayrton C Moreira AU - Margaret Castro Y1 - 2002/01/01 UR - http://www.jrheum.org/content/29/1/46.abstract N2 - OBJECTIVE: We evaluated the pattern of dexamethasone mediated inhibition of concanavalin-A (Con-A) stimulated peripheral blood mononuclear cell (PBMC) proliferation to classify patients with rheumatoid arthritis (RA) as corticosteroid resistant (CR) or sensitive (CS). We also studied the role of T helper 1, (Th1) and Th2 cytokines in the mechanism of glucocorticoid resistance in RA. METHODS: PBMC from 21 healthy controls and 15 patients with RA were isolated and cultured for the in vitro glucocorticoid sensitivity assay. Basal and Con-A stimulated PBMC proliferation levels and the inhibitory effect of different doses (10(-8), 10(-6), 10(-4) M) of dexamethasone (Dex) were evaluated. The IC50 was defined as the concentration of Dex that caused 50% inhibition of cell proliferation and subjects with an IC50 > 10(-6) M were considered to be CR. The supernatants were collected for cytokine [interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma)] measurement by ELISA. RESULTS: We observed lymphocyte proliferation after Con-A stimulation, which was inhibited by Dex in a dose-dependent manner in both groups. Two of 21 controls (9.5%) and 7/15 RA patients (53.3%) were CR (p < 0.01). Basal IL-4, IL-6, IL-10, and TNF-alpha levels were similar for both groups; however, basal IFN-gamma levels were slightly higher in patients with RA compared to controls. Con-A stimulation did not increase IL-4 or IL-6 levels compared to basal production but significantly increased IL-10 levels. IL-6 and IL-10 levels were significantly inhibited by Dex 10 M in both the control and RA groups. Con-A stimulation significantly increased TNF-alpha and IFN-gamma levels compared to the basal condition in the control and RA groups, and both cytokines were inhibited only by higher doses of Dex in the RA group. CONCLUSION: These findings might reflect a predominance of Th1 cells in RA that might contribute to corticosteroid resistance in patients in RA. ER -