Mechanisms of glucocorticoid reduction in asthmatic subjects treated with intravenous immunoglobulin

Background: Intravenous immunoglobulin (IVIG) has been used as an oral gluc ocorticoid (GC)-sparing agent in patients with steroid-dependent asthma, De spite its use, little is known regarding its mechanism of action. Objective: We sought to determine whether the GC-sparing effects of MG in s evere asthma are related to improved GC receptor (GCR)-binding affinity and subsequent enhanced GC sensitivity, Methods: In an open-label study, 11 steroid-dependent asthmatic subjects (6 GC-insensitive, 5 CC-sensitive) received monthly infusions of IVIG (2 g/kg ) for 6 months, Peak expiratory flow rates and oral GC dose were recorded d aily, and spirometry was performed monthly. Blood was drawn for lymphocyte stimulation assays and GCR assays at baseline and after 3 and 6 months of t herapy. Lymphocytes were stimulated ex vivo with PHA in the presence and ab sence of IVIG and increasing concentrations of dexamethasone (DEX). Results: MG resulted in significant reductions in oral GC dose (P <.02), nu mber of GC bursts (P =.033), and hospitalizations (P =.001) after 6 months of IVIG, Those with GC-insensitive asthma responded equally well to IVIG as those with GC-sensitive asthma. Associated with the improved clinical effi cacy, IVIG acted synergistically with DEX in suppressing lymphocyte activat ion as measured by a shift in the DEX dose-response curve by I log-fold (P =.03), IVIG therapy was also associated with significantly improved GCR-bin ding affinity (P =.01), Conclusions: IVIG resulted in significant reductions in oral GC requirement s and hospitalizations in a group of patients with severe asthma, with MG b eing as effective in patients with CC-insensitive asthma as in patients wit h GC-sensitive asthma, IVIG therapy acted synergistically with DEX in suppr essing lymphocyte activation and significantly improved GCR-binding affinit y after 3 and 6 months of therapy.