Mycophenolic acid inhibits SLE-associated cytokine expression and promotes apoptosis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus.
OBJECTIVE
To investigate the effect of the novel immunosuppressant mycophenolic acid (MPA) on cytokine production and apoptosis of the peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE).


METHODS
The levels of IL-10, IL-12, IFN-gamma, sFas and sFasL in the supernatants of cultured PBMC from 41 SLE patients was determined by the ABC-ELISA method. The percentage of IFN-gamma(+)IL-10(-), IFN-gamma(-)IL-10(+), and IFN-gamma(+)IL-10(+) subsets in CD4+ cells were detected by three-color flow cytometry. The percentage of apoptotic Th cells was detected by AV-FITC/PI flow cytometry. Samples from 22 sex- and age-comparable healthy people were used as normal controls.


RESULTS
The levels of IL-10, IL-12, and IFN-gamma were all significantly elevated in the supernatants of cultured PBMC from SLE samples, compared with normal controls. The enhanced productions of IL-10, IL-12, and IFN-gamma by PBMC from SLE both spontaneously and stimulated by phytohaemagglutinin (PHA) were significantly reduced by MPA. The percentages of CD4(+)IFN-gamma(-)IL-10(+) and CD4(+)IFN-gamma(+)IL-10(+) cell subsets in cultured PBMC from SLE were significantly increased, but decreased when MPA was added into the culture. After being cultured in vitro for 48 h, the PBMC of SLE patients showed a higher secretion of sFasL as well as a higher percentage of apoptosis. MPA significantly increased the apoptotic percentage of SLE PBMC, but reduced the secretion of sFasL and sFas.


CONCLUSIONS
MPA reduces the abnormal production of SLE-associated cytokines, such as IL-10, IL-12, and IFN-gamma; inhibits the increase of CD4(+)IFN-gamma(+)IL-10, CD4(+)IFN-gamma(-)IL-10(+) and CD4(+)IFN-gamma(+)IL-10(+) subset; and promotes the apoptosis of PBMC in SLE patients, which may be associated with the therapeutic mechanism of MPA for SLE.
Su
Ding-Lei
DL
Department of Immunology, Nanjing Medical University, Nanjing 210029, China.
Wang
Hui-Juan
HJ
Ji
Xiao-Hui
XH
Li
Yuan-Yuan
YY
Xuan
Heng-Bao
HB
Heng
Chun
C
Li
Yu-Feng
YF
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000494:pharmacology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D009173:Mycophenolic Acid