Inhibitory effect of Cyclosporin A and corticosteroids on the production of IFN-gamma and IL-17 by T cells in Vogt-Koyanagi-Harada syndrome.
Cyclosporin A (CsA) and corticosteroids are extensively used in the treatment of autoimmune diseases including Vogt-Koyanagi-Harada (VKH) syndrome. The exact immunosuppressive mechanisms of these drugs are not exactly known. Th1 and Th17 cells are important populations involved in autoimmune diseases. In this study, we investigated whether they are involved in VKH syndrome and how their function is affected by CsA and corticosteroids. The results showed that IL-17, IFN-gamma, RORgammat and T-bet were upregulated in patients with active uveitis. CsA and corticosteroids were able to downregulate all these elevated levels which correlated with the clinical improvement of the uveitis. In vitro experiments showed that CsA and dexamethasone could decrease the frequencies of Th1 and Th17 cells and inhibit IL-17 and IFN-gamma production. These data suggest that an upregulated Th1 and Th17 response is associated with active VKH syndrome. CsA and corticosteroids may exert their immunosuppressive role by downregulating Th1 and Th17 cells.
Liu
Xiaoli
X
Uveitis Study Center, Zhongshan Ophthalmic Center, Sun Yat-sen University, State Key Laboratory of Ophthalmology, International Uveitis Study Laboratory of Guangdong Province, Guangzhou, P.R. China.
Yang
Peizeng
P
Lin
Xiaomin
X
Ren
Xiangrong
X
Zhou
Hongyan
H
Huang
Xiangkun
X
Chi
Wei
W
Kijlstra
Aize
A
Chen
Ling
L
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects; D014607:Uveomeningoencephalitic Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D012333:RNA, Messenger; D007371:Interferon-gamma; D016572:Cyclosporine