| Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids. | |
MedLine Citation:
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PMID: 9776479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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T Hirano; M Homma; K Oka; H Tsushima; T Niitsuma; T Hayashi |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Immunopharmacology Volume: 40 ISSN: 0162-3109 ISO Abbreviation: Immunopharmacology Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1998-12-17 Completed Date: 1998-12-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902474 Medline TA: Immunopharmacology Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 57-66 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. hiranot@ps.toyaku.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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