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Production of interleukin-17 in Behcet's disease is inhibited by cyclosporin A.

Chi W, Yang P, Zhu X, Wang Y, Chen L, Huang X, Liu X - Mol. Vis. (2010)

Bottom Line: The results showed that significantly higher levels of IL-17 and IFN-gamma were observed in active BD patients as compared with controls.However, CSA did not influence the CD69 expression in CD4(+) and CD8(+) T cells induced by phorbol 12-myristate,13-acetate (PMA) ionomycin.The results suggested that the inhibitory effect of CsA on uveitis in BD patients may be partially mediated through inhibiting the production of IL-17 and IFN-gamma.

View Article: PubMed Central - PubMed

Affiliation: Zhongshan Ophthalmic Centric, Sun Yat-sen University, Guangzhou, P.R. China.

ABSTRACT

Purpose: Behcet's disease (BD) is a systemic inflammatory disease presumably caused by an autoimmune response. Interleukin (IL)-17 has been demonstrated to be involved in the development and maintenance of certain inflammatory diseases, including BD. This study was designed to investigate the influence of cyclosporine A (CsA) on IL-17 production by peripheral blood mononuclear cells (PBMCs) from BD patients in vitro and in vivo.

Methods: Fifteen BD patients with active uveitis were involved in this study. Blood samples were taken from these patients for analysis of IL-17 and interferon (IFN)-gamma. Six patients were re-evaluated at 1 and 3 months after treatment with CsA. The levels of IL-17 and IFN-gamma in the supernatants of PBMCs from patients before treatment cultured without or with CsA at different concentrations were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to evaluate the frequencies of IL-17-producing and IFN-gamma-producing T cells and the expression of CD69 on CD4(+) or CD8(+) T cells before, 1, and 3 months after CsA treatment.

Results: The results showed that significantly higher levels of IL-17 and IFN-gamma were observed in active BD patients as compared with controls. Treatment with CsA could inhibit the production of both cytokines in association with an amelioration of intraocular inflammation. In vitro, CsA significantly inhibited the production of IL-17 and IFN-gamma by PBMCs activated with anti-CD3 and anti-CD28 antibodies or phorbol 12-myristate,13-acetate and ionomycin in BD patients with active uveitis. However, CSA did not influence the CD69 expression in CD4(+) and CD8(+) T cells induced by phorbol 12-myristate,13-acetate (PMA) ionomycin.

Conclusions: Our findings showed that CsA can significantly inhibit the intraocular inflammation of BD patients and the expression of IL-17 and IFN-gamma in vivo and in vitro. The results suggested that the inhibitory effect of CsA on uveitis in BD patients may be partially mediated through inhibiting the production of IL-17 and IFN-gamma.

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The effect of cyclosporin A on the percentages of interleukin-17-producing and interferon-γ-producing T cells from patients with Behcet’s disease and normal controls in vitro. Isolated peripheral blood mononuclear cells (1×106 cells/ml) were stimulated with phorbol 12-myristate,13-acetate/ionomycin for 6 h in the absence or presence of CsA (50 ng/ml). The percentage of both IL-17-producing and IFN-γ-producing CD4+ or CD8+ T cells was significantly higher in BD patients than in normal controls and was significantly reduced in the presence of CsA. Data are expressed as means±SD.
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f3: The effect of cyclosporin A on the percentages of interleukin-17-producing and interferon-γ-producing T cells from patients with Behcet’s disease and normal controls in vitro. Isolated peripheral blood mononuclear cells (1×106 cells/ml) were stimulated with phorbol 12-myristate,13-acetate/ionomycin for 6 h in the absence or presence of CsA (50 ng/ml). The percentage of both IL-17-producing and IFN-γ-producing CD4+ or CD8+ T cells was significantly higher in BD patients than in normal controls and was significantly reduced in the presence of CsA. Data are expressed as means±SD.

Mentions: Isolated PBMCs from BD patients and normal controls were stimulated with PMA (20 ng/ml) and ionomycin (1 µg/ml) for 6 h in the presence of CsA (50 ng/ml) to study the regulatory effect of CsA on IL-17 and IFN-γ production. The results showed that CsA could significantly lower the frequencies of IL-17 and IFN-γ in CD4+ and CD8+ T cells from both BD patients and normal controls (Figure 3). However, CsA did not influence the expression of CD69 in CD4+ and CD8+ T cells induced by PMA and ionomycin (Figure 4A,B).


Production of interleukin-17 in Behcet's disease is inhibited by cyclosporin A.

Chi W, Yang P, Zhu X, Wang Y, Chen L, Huang X, Liu X - Mol. Vis. (2010)

The effect of cyclosporin A on the percentages of interleukin-17-producing and interferon-γ-producing T cells from patients with Behcet’s disease and normal controls in vitro. Isolated peripheral blood mononuclear cells (1×106 cells/ml) were stimulated with phorbol 12-myristate,13-acetate/ionomycin for 6 h in the absence or presence of CsA (50 ng/ml). The percentage of both IL-17-producing and IFN-γ-producing CD4+ or CD8+ T cells was significantly higher in BD patients than in normal controls and was significantly reduced in the presence of CsA. Data are expressed as means±SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875255&req=5

f3: The effect of cyclosporin A on the percentages of interleukin-17-producing and interferon-γ-producing T cells from patients with Behcet’s disease and normal controls in vitro. Isolated peripheral blood mononuclear cells (1×106 cells/ml) were stimulated with phorbol 12-myristate,13-acetate/ionomycin for 6 h in the absence or presence of CsA (50 ng/ml). The percentage of both IL-17-producing and IFN-γ-producing CD4+ or CD8+ T cells was significantly higher in BD patients than in normal controls and was significantly reduced in the presence of CsA. Data are expressed as means±SD.
Mentions: Isolated PBMCs from BD patients and normal controls were stimulated with PMA (20 ng/ml) and ionomycin (1 µg/ml) for 6 h in the presence of CsA (50 ng/ml) to study the regulatory effect of CsA on IL-17 and IFN-γ production. The results showed that CsA could significantly lower the frequencies of IL-17 and IFN-γ in CD4+ and CD8+ T cells from both BD patients and normal controls (Figure 3). However, CsA did not influence the expression of CD69 in CD4+ and CD8+ T cells induced by PMA and ionomycin (Figure 4A,B).

Bottom Line: The results showed that significantly higher levels of IL-17 and IFN-gamma were observed in active BD patients as compared with controls.However, CSA did not influence the CD69 expression in CD4(+) and CD8(+) T cells induced by phorbol 12-myristate,13-acetate (PMA) ionomycin.The results suggested that the inhibitory effect of CsA on uveitis in BD patients may be partially mediated through inhibiting the production of IL-17 and IFN-gamma.

View Article: PubMed Central - PubMed

Affiliation: Zhongshan Ophthalmic Centric, Sun Yat-sen University, Guangzhou, P.R. China.

ABSTRACT

Purpose: Behcet's disease (BD) is a systemic inflammatory disease presumably caused by an autoimmune response. Interleukin (IL)-17 has been demonstrated to be involved in the development and maintenance of certain inflammatory diseases, including BD. This study was designed to investigate the influence of cyclosporine A (CsA) on IL-17 production by peripheral blood mononuclear cells (PBMCs) from BD patients in vitro and in vivo.

Methods: Fifteen BD patients with active uveitis were involved in this study. Blood samples were taken from these patients for analysis of IL-17 and interferon (IFN)-gamma. Six patients were re-evaluated at 1 and 3 months after treatment with CsA. The levels of IL-17 and IFN-gamma in the supernatants of PBMCs from patients before treatment cultured without or with CsA at different concentrations were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to evaluate the frequencies of IL-17-producing and IFN-gamma-producing T cells and the expression of CD69 on CD4(+) or CD8(+) T cells before, 1, and 3 months after CsA treatment.

Results: The results showed that significantly higher levels of IL-17 and IFN-gamma were observed in active BD patients as compared with controls. Treatment with CsA could inhibit the production of both cytokines in association with an amelioration of intraocular inflammation. In vitro, CsA significantly inhibited the production of IL-17 and IFN-gamma by PBMCs activated with anti-CD3 and anti-CD28 antibodies or phorbol 12-myristate,13-acetate and ionomycin in BD patients with active uveitis. However, CSA did not influence the CD69 expression in CD4(+) and CD8(+) T cells induced by phorbol 12-myristate,13-acetate (PMA) ionomycin.

Conclusions: Our findings showed that CsA can significantly inhibit the intraocular inflammation of BD patients and the expression of IL-17 and IFN-gamma in vivo and in vitro. The results suggested that the inhibitory effect of CsA on uveitis in BD patients may be partially mediated through inhibiting the production of IL-17 and IFN-gamma.

Show MeSH
Related in: MedlinePlus