Mycophenolic acid inhibits SLE-associated cytokine expression and promotes apoptosis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus1

Abstract

Aim: To investigate the effect of the novel immunosuppressant mycophenolic acid (MPA) on cytokine production and apoptosis of the peripheral blood mono‐nuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE). Methods: The levels of IL‐10, IL‐12, IFN‐γ, sFas and sFasL in the supernatants of cultured PBMC from 41 SLE patients was determined by the ABC‐ELISA method. The percentage of IFN‐γ+IL‐10−, IFN‐γ−IL‐10+, and IFN‐γ+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‐γ 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‐γ by PBMC from SLE both spontaneously and stimulated by phytohaemagglutinin (PHA) were significantly reduced by MPA. The percentages of CD4+IFN‐γ−IL‐10+ and CD4+IFN‐γ+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. Conclusion: MPA reduces the abnormal production of SLE‐associated cytokines, such as IL‐10, IL‐12, and IFN‐γ; inhibits the increase of CD4+IFN‐γ+IL‐10, CD4+IFN‐γ−IL‐10+ and CD4+IFN‐γ+IL‐10+ subset; and promotes the apoptosis of PBMC in SLE patients, which may be associated with the therapeutic mechanism of MPA for SLE.

Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus

“…Finally, because our SLE patients were receiving different treatments and some drugs such as antimalarials (38–40) or immunosuppressive agents (41) have been reported to influence cytokine production, we investigated if the cytokine imbalance observed in our patients might be associated with the treatment they were receiving. No differences were found both in the soluble cytokine levels and in the intracellular expression in T lymphocytes among all groups when considering all treatments the patients were receiving, although, because a small number of patients were included in each group, more studies are needed to confirm these preliminary results and to clarify the influence of treatment on the cytokine production in SLE.…”

Value of combined detection of anti‑nuclear antibody, anti‑double‑stranded DNA antibody and C3, C4 complements in the clinical diagnosis of systemic lupus erythematosus

“…The disease occurs in young women of childbearing age and the prevalence of females accounts for 90% of the total number of affected patients. The peak age of the disease is 15–40 years (3,4). SLE usually affects the whole body, and there are multiple autoantibodies in the patient's serum as clinical features.…”

Effective plasma concentrations of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in the remission-maintenance phase

“…[3][4][5] These improvements are more likely due to MMF and not to prednisolone as the daily dose of the steroid decreased significantly with MMF administration. A possible mechanism for MPA's effect in SLE, as suggested by Su et al, 24 is the modulation of cytokine expression (interleukin-10 and interleukin-12 and interferon-c) by MPA. Jiang et al 25 reported that enhanced interleukin-10 promoted B-cell proliferation and differentiation and stimulated the production of pathogenic anti-DNA antibody.…”

“…A possible mechanism for MPA’s effect in SLE, as suggested by Su et al. ,24 is the modulation of cytokine expression (interleukin‐10 and interleukin‐12 and interferon‐γ) by MPA. Jiang et al.…”