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

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.

• Authors: M Seki, C Ushiyama, N Seta, K Abe, T Fukazawa, J Asakawa, Y Takasaki, H Hashimoto
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 41 Issue 5 Pg. 823-30 (May 1998) ISSN: 0004-3591 [Print] United States
• PMID: 9588733 (Publication Type: Comparative Study, Journal Article)

Chemical References

• CD4 Antigens
• CD8 Antigens
• Glucocorticoids
• Proto-Oncogene Proteins c-bcl-2
• fas Receptor
• Prednisolone

Topics

• Adolescent
• Adult
• Apoptosis (drug effects, physiology)
• CD4 Antigens (metabolism)
• CD8 Antigens (metabolism)
• Cell Culture Techniques
• Cell Survival
• Drug Resistance
• Female
• Flow Cytometry
• Glucocorticoids (therapeutic use)
• Humans
• Lupus Erythematosus, Systemic (drug therapy, physiopathology)
• Middle Aged
• Monocytes (drug effects, physiology)
• Prednisolone (therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• T-Lymphocytes (drug effects, physiology)
• fas Receptor (metabolism)