Document Detail


Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids.
MedLine Citation:
PMID:  9776479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucocorticoids (GCs) are known to be effective for bronchial asthma, however, a considerable number of asthma patients fail to respond to GC despite the onset of serious side effects. Here we examined individual sensitivities to five clinically-used GCs in 40 asthma patients and 100 healthy subjects. Peripheral-blood mononuclear cells (PBMCs) were isolated from these subjects, and their in vitro sensitivities to hydrocortisone, prednisolone, methylprednisolone, dexamethasone, and betamethasone were determined with a mitogen-assay procedure. The number of PBMCs positive to IL-2 receptors (IL-2Rs) as well as soluble IL-2R (sIL-2R) levels in serum were concomitantly measured in asthma patients, and relationships between these cytokine indices and PBMC-sensitivities to GCs were also examined. Large individual variations in GC IC50s have been observed in PBMCs from asthma subjects, especially in prednisolone IC50s (ranged from 1 to 10,000 ng/ml). When compared with healthy subjects, asthma patients tend to show PBMC-resistance to prednisolone (p < 0.05). Moreover, potencies of methylprednisolone on PBMC-blastogenesis were > 10 times higher than those of prednisolone in both healthy subjects and asthmatics (p < 0.01). In asthma patients, IC50s of hydrocortisone, prednisolone and betamethasone against PBMC-blastogenesis were significantly correlated with elevated percentages of IL-2R-positive PBMCs (p < 0.05), while the IC50 of methylprednisolone showed no such correlation. sIL-2R levels did not correlate with IC50s of any of the GCs examined. Thus, the results showed that a part of asthma patients exhibited PBMC-resistance to GCs, especially to prednisolone. Methylprednisolone potency was unexpectedly higher (> 10 times) than prednisolone potency. Our results also raised the possibility that PBMC-resistance to prednisolone in asthma may correlate with an increase in IL-2R positive PBMCs.
Authors:
T Hirano; M Homma; K Oka; H Tsushima; T Niitsuma; T Hayashi
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunopharmacology     Volume:  40     ISSN:  0162-3109     ISO Abbreviation:  Immunopharmacology     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-12-17     Completed Date:  1998-12-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902474     Medline TA:  Immunopharmacology     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  57-66     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. hiranot@ps.toyaku.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Anti-Asthmatic Agents / administration & dosage,  pharmacology,  therapeutic use*
Asthma / drug therapy*,  immunology
Dexamethasone / therapeutic use
Female
Glucocorticoids / administration & dosage,  pharmacology,  therapeutic use*
Humans
Hydrocortisone / therapeutic use
Lymphocyte Activation / drug effects
Male
Methylprednisolone / therapeutic use
Middle Aged
Prednisolone / therapeutic use
Receptors, Interleukin-2 / blood*
Structure-Activity Relationship
T-Lymphocytes / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Anti-Asthmatic Agents; 0/Glucocorticoids; 0/Receptors, Interleukin-2; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 50-24-8/Prednisolone; 83-43-2/Methylprednisolone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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