Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids.
Immunopharmacology
; 40(1): 57-66, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9776479
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Linfócitos T
/
Receptores de Interleucina-2
/
Antiasmáticos
/
Glucocorticoides
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article