Mechanisms of glucocorticoid reduction in asthmatic subjects treated with intravenous immunoglobulin

J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):421-6. doi: 10.1016/s0091-6749(99)70466-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Dexamethasone / pharmacology
  • Drug Evaluation
  • Drug Resistance
  • Drug Synergism
  • Female
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / pharmacology*
  • Immunoglobulins, Intravenous / therapeutic use
  • Lymphocyte Activation
  • Male
  • Prednisone / administration & dosage*
  • Prednisone / pharmacology
  • Prednisone / therapeutic use
  • Receptors, Glucocorticoid / drug effects
  • Spirometry
  • Treatment Outcome
  • Vital Capacity


  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Immunoglobulins, Intravenous
  • Receptors, Glucocorticoid
  • Dexamethasone
  • Prednisone