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Titolo:
APOPTOSIS OF LYMPHOCYTES INDUCED BY GLUCOCORTICOIDS AND RELATIONSHIP TO THERAPEUTIC EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS
Autore:
SEKI M; USHIYAMA C; SETA N; ABE K; FUKAZAWA T; ASAKAWA J; TAKASAKI Y; HASHIMOTO H;
Indirizzi:
JUNTENDO UNIV,SCH MED,DEPT INTERNAL MED,DIV RHEUMATOL,BUNKYO KU,2-1-1HONGO TOKYO 113 JAPAN
Titolo Testata:
Arthritis and rheumatism
fascicolo: 5, volume: 41, anno: 1998,
pagine: 823 - 830
SICI:
0004-3591(1998)41:5<823:AOLIBG>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-DEATH; DNA FRAGMENTATION; HUMAN THYMOCYTES; TRANSGENIC MICE; T-LYMPHOCYTES; IL-2 PROTECTS; DISEASE; AFFINITY; BCL-2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
M. Seki et al., "APOPTOSIS OF LYMPHOCYTES INDUCED BY GLUCOCORTICOIDS AND RELATIONSHIP TO THERAPEUTIC EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS", Arthritis and rheumatism, 41(5), 1998, pp. 823-830

Abstract

Objective. Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease insome patients is resistant to these agents, This study evaluated the possibility of a relationship between response to GC treatment and therate of apoptosis in vitro, and also analyzed Bcl-2 and Fas expression on peripheral blood mononuclear cells (PBMC) from patients with SLE in relation to GC-induced apoptosis. Methods. Twenty-seven SLE patients and 13 normal controls were studied. Disease activity scores were determined before and after treatment and used to divide patients into 2groups: GC-resistant and GC-responsive. Isolated PBMC were stimulatedwith anti-CD3 monoclonal antibodies, cultured with various concentrations of GC, and analyzed by alamar blue assay to determine the LC50, defined as the concentration of GC lethal to 50% of the cells. We measured the expression of CD4, CD8, Fas, and Bcl-2 by FACStar plus flow cytometry. Results, Lymphocytes in the GC-resistant group of SLE patients showed a significantly lower percentage of GC-induced apoptotic cells than did lymphocytes from the responsive group or from normal controls. The LC,, in the resistant group was significantly higher than thatin normal controls or the responsive group. The lymphocytes remainingin the resistant group after GC treatment were mainly CD8+, with a high expression of Bcl-2. There was no significant difference in Fas expression between the GC-responsive and GC-resistant groups. Conclusion. Determination of the LC50 may be useful in predicting the efficacy ofGC treatment in SLE patients, and may be of use in considering other treatment options. CD8 and Bcl-2 double-positive lymphocytes that are insensitive to the apoptotic effect of GCs may play a role in the resistance to these agents in SLE patients.

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Documento generato il 30/11/20 alle ore 19:41:04