Evaluation of CD4(+)CD25(+)FoxP3(+) T cell populations, IL-10 production, and their correlation with clinical and biochemical parameters in sickle cell anemia patients with leg ulcers.

Leg ulcers (LUs) are a debilitating complication of sickle cell anemia (SCA), with inflammation known to play a crucial role in their pathogenesis. Many studies have described the roles of T helper type 1 (Th1) and Th2 pathways in SCA; however, defects in anti-inflammatory responses are poorly understood. We evaluated interleukin (IL)-10 levels in serum and peripheral blood mononuclear cells (PBMCs) in SCA patients with leg ulcers (SCALU) and without leg ulcers (SCAWH) in addition to CD4(+) CD25(+)FoxP3(+) T cell populations and their its IL-10 expression. In stimulated and unstimulated PBMC cultures, SCALU patients produced higher levels of IL-10 than those in the SCAWH group. Higher levels of IL-10 in SCALU patients correlated with a history of osteonecrosis in stimulated and unstimulated cultures when compared with those in SCAWH. Immunophenotyping revealed that SCALU patients had a higher proportion of CD4(+)CD25(+)FoxP3(+), Tr1 and CD4(+)CD25(+)FoxP3(+)IL-10(+) T cells than other groups. Our findings revealed that IL-10 levels were increased in unstimulated cells from the SCALU group, and that this group also presented with a predominant CD4(+) CD25(+)FoxP3(+) cell population despite many of those cells being IL-10 negative.

Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.

OBJECTIVE AND DESIGN: To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients. METHODS: The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire. RESULTS: The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 µM, p = 0.0005; p < 0.0001; p < 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 µM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS28 >5.1 and CDAI >22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively). CONCLUSION: The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.