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Abstract: A small proportion of asthma patients do not obtain full benefit from corticosteroid therapy. Corticoresistant asthmatics do not demonstrate benefit in lung function following a course of oral prednisolone for two weeks, and corticosteroid-dependent asthmatics need chronic oral prednisolone to maintain some degree of control and are often patients with severe asthma. The mechanisms by which the effect of corticosteroids are blunted in some patients with asthma have been evaluated mainly in circulating blood cells. The poor clinical response to corticosteroids is also reflected in the reduced anti-inflammatory effects of steroids on cell activation. The mechanisms of poor response include the production of glucocorticoid receptor (GR)-β receptor that competes with the active natural GRα receptor, binding of GRα with inflammatory transcription factors, defect of translocation of activated GRα into the nucleus, phosphorylation of GRα for diminished binding affinity by IL-2 and IL-4, and defect in recruitment of histone deacetylase-2 to the activated transcriptional complex. A solution to corticosteroid resistance in corticosteroid-resistant or -dependent asthmatics should be possible by using possible drug targets as indicated by these mechanisms. However, much more work is needed. [Copyright &y& Elsevier]

Abstract: The results provide new insights into the role of IL-2/IL-2R pathway in DC. We report that stimulation of human monocyte-derived DC with LPS strongly upregulated CD25 (α chain of the IL-2R) expression. In addition, by using a humanized monoclonal antibody against CD25, we demonstrated that the IL-2 signalling in DC upregulated both IL-12 and γIFN production but decreased IL-10 synthesis. Anti-CD25 treatment reduced the ability of LPS-DC to induce allogeneic CD4+ T cell proliferation as compared to LPS-matured DC. In addition, LPS-matured DC treated with IL-2 had a higher allostimulatory capacity compared to LPS-DC. We also found that LPS-matured DC produced IL-2. Thus, IL-2 seems to contribute actively to DC activation through an autocrine pathway. Moreover, IL-2 pathway in DC is involved in T helper priming. These findings might be useful for protocols in cellular therapy and a valuable tool to understand graft rejection versus the acquisition of peripheral tolerance. [Copyright &y& Elsevier]