Background: Intravenous immunoglobulin (IVIG) has been used as an oral glucocorticoid (GC)-sparing agent in patients with steroid-dependent asthma. Despite its use, little is known regarding its mechanism of action.
Objective: We sought to determine whether the GC-sparing effects of IVIG in severe 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 GC-sensitive) received monthly infusions of IVIG (2 g/kg) for 6 months. Peak expiratory flow rates and oral GC dose were recorded daily, and spirometry was performed monthly. Blood was drawn for lymphocyte stimulation assays and GCR assays at baseline and after 3 and 6 months of therapy. Lymphocytes were stimulated ex vivo with PHA in the presence and absence of IVIG and increasing concentrations of dexamethasone (DEX).
Results: IVIG resulted in significant reductions in oral GC dose (P <.02), number 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 efficacy, IVIG acted synergistically with DEX in suppressing lymphocyte activation as measured by a shift in the DEX dose-response curve by 1 log-fold (P =.03). IVIG therapy was also associated with significantly improved GCR-binding affinity (P =.01).
Conclusions: IVIG resulted in significant reductions in oral GC requirements and hospitalizations in a group of patients with severe asthma, with IVIG being as effective in patients with GC-insensitive asthma as in patients with GC-sensitive asthma. IVIG therapy acted synergistically with DEX in suppressing lymphocyte activation and significantly improved GCR-binding affinity after 3 and 6 months of therapy.