BACKGROUND: Concomitant @entity1499 ( @entity1500 ) therapy of severe, oral corticosteroid-dependent @entity748 has been shown to be corticosteroid sparing, but the mechanism is unknown. We hypothesized that @entity1500 therapy of these @entity1 increases the susceptibility of their T cells to corticosteroid inhibition. OBJECTIVE: To measure @entity617 inhibition of lectin-induced proliferation of peripheral blood T cells from a group of these @entity1 before, during and following @entity1500 therapy. METHODS: Eighteen severe @entity748 (median (range) age 56 (33-68) years, FEV1 61 (38-69)% predicted, dependent on oral @entity617 15 (7.5-25) mg/day in addition to high-dose, inhaled corticosteroids) were treated with @entity1500 15 mg intramuscularly, weekly for 28 weeks. After 12 weeks of @entity1500 , oral @entity617 dosages were reduced systematically over 16 weeks, provided that @entity565 control did not deteriorate. @entity1 were followed for a further 12 weeks after @entity1500 withdrawal. Concentration-dependent, @entity617 inhibition of lectin-induced proliferation of peripheral blood T cells was measured just prior to @entity1500 therapy (week 1) and at weeks 12, 28 and 40, and IC50 concentrations were interpolated. RESULTS: By week 28 of @entity1500 therapy, @entity1 were able to reduce oral @entity617 dosages from (median, SIQR) 15 (10-20.5) to 5.9 (1.4-9.4) mg/day (P<0.01) without alteration of lung function and symptoms, while median IC50 values for @entity617 inhibition of peripheral blood T cell proliferation were reduced from 49 (21-144) to 4 (1-9) nm (P<0.0001). These increased again to 15 (9.4-25.7) mg/day and 36 (18-67) nm, respectively, following @entity1500 withdrawal. A correlation (P<0.01) was observed between percentage reductions in @entity617 dosages in vivo and fold changes in @entity617 IC50in vitro between weeks 12 and 28. CONCLUSION: This effect of @entity1500 may at least partly account for its oral corticosteroid-sparing effect in severe @entity565 .

XXXX therapy in asthma increases T cell susceptibility to corticosteroid inhibition.

@entity748 :: ('MESH:D013224', 'Disease') :: ['asthmatics'] @entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity1500 :: ('CHEBI:44185', 'Chemical') :: ['MTX'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate'] @entity617 :: ('MESH:D011239', 'Chemical') :: ['prednisolone']
@entity1499 :: (MESH:D008727,Chemical) :: ['Methotrexate']
