PMID- 10069875
OWN - NLM
STAT- MEDLINE
DCOM- 19990402
LR  - 20190723
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 103
IP  - 3 Pt 1
DP  - 1999 Mar
TI  - Mechanisms of glucocorticoid reduction in asthmatic subjects treated with 
      intravenous immunoglobulin.
PG  - 421-6
AB  - 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.
FAU - Spahn, J D
AU  - Spahn JD
AD  - Division of Clinical Pharmacology, Ira J. and Jacqueline Neimark Laboratory of 
      Clinical Pharmacology in Pediatrics, Department of Pediatrics, National Jewish 
      Medical and Research Center, Denver, Colo. 80206, USA.
FAU - Leung, D Y
AU  - Leung DY
FAU - Chan, M T
AU  - Chan MT
FAU - Szefler, S J
AU  - Szefler SJ
FAU - Gelfand, E W
AU  - Gelfand EW
LA  - eng
GR  - AI-41022/AI/NIAID NIH HHS/United States
GR  - HL-36577/HL/NHLBI NIH HHS/United States
GR  - HL-37260/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Glucocorticoids)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Anti-Asthmatic Agents/*administration & dosage/pharmacology/therapeutic use
MH  - Anti-Inflammatory Agents/*administration & dosage/pharmacology/therapeutic use
MH  - Asthma/*drug therapy
MH  - Dexamethasone/pharmacology
MH  - Drug Evaluation
MH  - Drug Resistance
MH  - Drug Synergism
MH  - Female
MH  - Forced Expiratory Volume
MH  - Glucocorticoids/*administration & dosage/pharmacology/therapeutic use
MH  - Humans
MH  - Immunoglobulins, Intravenous/administration & dosage/*pharmacology/therapeutic 
      use
MH  - Lymphocyte Activation
MH  - Male
MH  - Prednisone/*administration & dosage/pharmacology/therapeutic use
MH  - Receptors, Glucocorticoid/drug effects
MH  - Spirometry
MH  - Treatment Outcome
MH  - Vital Capacity
EDAT- 1999/03/09 00:00
MHDA- 1999/03/09 00:01
CRDT- 1999/03/09 00:00
PHST- 1999/03/09 00:00 [pubmed]
PHST- 1999/03/09 00:01 [medline]
PHST- 1999/03/09 00:00 [entrez]
AID - S0091-6749(99)70466-5 [pii]
AID - 10.1016/s0091-6749(99)70466-5 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):421-6. doi: 
      10.1016/s0091-6749(99)70466-5.