Production of interleukin-17 in Behcet's disease is inhibited by cyclosporin A.
OBJECTIVE
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.
Zhongshan Ophthalmic Centric, Sun Yat-sen University, Guangzhou, P.R. China.
Wei
W
Chi
Peizeng
P
Yang
Xuefei
X
Zhu
Yuqin
Y
Wang
Lina
L
Chen
Xiangkun
X
Huang
Xiaoli
X
Liu
D000328:Adult; D001528:Behcet Syndrome / Q000097:blood*; D016572:Cyclosporine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D007166:Immunosuppressive Agents; D020381:Interleukin-17; D007371:Interferon-gamma; D016572:Cyclosporine