Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus

Manami Seki, Chifuyu Ushiyama, Noriyuki Seta, Kaori Abe, Toru Fukazawa, Junichi Asakawa, Yoshinari Takasaki, Hiroshi Hashimoto

Research output: Contribution to journalArticle

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Abstract

Objective. Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate 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 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with 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 LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in 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 of GC 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.

Original languageEnglish
Pages (from-to)823-830
Number of pages8
JournalArthritis and Rheumatism
Volume41
Issue number5
DOIs
Publication statusPublished - 1998 May

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Systemic Lupus Erythematosus
Glucocorticoids
Lymphocytes
Apoptosis
Therapeutics
Blood Cells
Flow Cytometry
Monoclonal Antibodies

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. / Seki, Manami; Ushiyama, Chifuyu; Seta, Noriyuki; Abe, Kaori; Fukazawa, Toru; Asakawa, Junichi; Takasaki, Yoshinari; Hashimoto, Hiroshi.

In: Arthritis and Rheumatism, Vol. 41, No. 5, 05.1998, p. 823-830.

Research output: Contribution to journalArticle

Seki, Manami ; Ushiyama, Chifuyu ; Seta, Noriyuki ; Abe, Kaori ; Fukazawa, Toru ; Asakawa, Junichi ; Takasaki, Yoshinari ; Hashimoto, Hiroshi. / Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. In: Arthritis and Rheumatism. 1998 ; Vol. 41, No. 5. pp. 823-830.
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abstract = "Objective. Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate 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 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with 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 LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in 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 of GC 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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AU - Seki, Manami

AU - Ushiyama, Chifuyu

AU - Seta, Noriyuki

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AU - Fukazawa, Toru

AU - Asakawa, Junichi

AU - Takasaki, Yoshinari

AU - Hashimoto, Hiroshi

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N2 - Objective. Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate 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 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with 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 LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in 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 of GC 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.

AB - Objective. Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate 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 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with 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 LC50 in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in 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 of GC 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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