We have identified a small molecular weight compound, SCH 14988, which specifically stimulates in vitro granulocyte-colony stimulating factor (G-CSF ) production from activated human peripheral blood mononuclear cells and monocytes but not other cytokines or CSFs with hematoregulatory activity. In vivo administration of SCH 14988 to mice rendered neutropenic by cyclophosphamide treatment resulted in the accelerated recovery of the peripheral neutrophil compartment. This activity correlated with increased in vivo G-CSF levels and stimulation of marrow granulopoiesis, and was comparable to that of exogenously administered recombinant human G-CSF. No alterations to other leukocyte populations in peripheral blood, spleen, or the peritoneal cavity were observed. These findings suggest that SCH 14988 may be clinically useful to enhance neutrophil granulopoiesis, as well as to study the mechanisms involved in G-CSF gene regulation.
BackgroundIt is generally considered that B cells regulate immune response mainly through producing specific antibodies or a variety of cytokines., but recent studies have found that the lack of B cells and CDl9 –/– mice in experimental autoimmune encephalomyelitis (EAE) mouse model is more serious, and in T cell mediated inflammation experiment, CDl9–/– mice show a more serious contact hypersensitivity (CHS). Therefore, it indicated that B cells also play an important role in the negative immune regulation.ObjectivesTo investigate the expression of regulatory B cells (Bregs) in peripheral blood of patients with systemic lupus erythematosus (SLE) and the function of Bregs in the pathogenesis of SLE.MethodsThirty-eight active SLE patients, twenty-two inactive SLE patients and twenty healthy controls were enrolled in this study. The expression of IL-10+CD19+Breg and CD19+CD24hiCD38hiBreg in peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometric analysis. IL-10 was measured in the culture supermatants by ELISA.ResultsThe expression of IL-10+CD19+Breg in PBMCs of active SLE patients was 1.54±0.64%, lower than those in inactive SLE patients (2.42±0.75)% (P<0.001) and healthy controls (4.35±1.00)% (P<0.001). And the expression of CD19+CD24hiCD38hiBreg was 1.26±0.45%, also lower than those in inactive SLE patients (2.01±0.61)% (P<0.001) and healthy controls (3.14±0.87)% (P<0.001). The level of IL-10 in the culture supermatants of active SLE patients significantly decreased, which was lower than those in inactive SLE patients (P<0.05) and healthy controls (P<0.001). The percentage of IL-10+CD19+Breg and CD19+CD24hiCD38hiBreg in peripheral blood of SLE patients was positively correlated with the level of IL-10 in the culture supermatants (r=0.652, P<0.001 and r=0.574,P<0.001).ConclusionsExpression of IL-10 related Bregs was significantly decreased in peripheral blood of active SLE patients. Bregs may play a critical role in the pathogenesis of SLE.Disclosure of InterestNone declared
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