Mechanisms of glucocorticoid reduction in asthmatic subjects treated with intravenous immunoglobulin.

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.