The expression of cytokines in the aqueous humor and serum during endotoxin-induced uveitis in C3H/HeN mice.
OBJECTIVE
The cytokines present in the aqueous humor and serum of C3H/HeN mice with endotoxin-induced acute anterior uveitis were analyzed, and the potential role of the cytokines in the pathogenesis of the disease was investigated.


METHODS
One hundred and eighty C3H/HeN mice were divided into an experimental group (n=150) and a control group (n=30). The mice in the experimental group were footpad-injected with 200 microg Vibro cholerae endotoxin (classical biotype, serotype Ogawa). The mice were then executed 4 h, 8 h, 16 h, 24 h, and 48 h after the injection of endotoxin. Aqueous humor and peripheral blood samples were collected using a microinjector. Ten samples were pooled together for analysis and centrifuged at 705x g, at 4 degrees C, for 3 min. The supernatant was collected and stored at -80 degrees C. The concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-gamma (IFN-gamma) in the samples were measured using a Cytometric Bead Array (CBA).


RESULTS
Acute anterior uveitis was successfully induced in C3H/HeN mice. At roughly 16 h post-injection, the concentrations of both IL-1 and IL-6 reached peak levels, and were significantly different from the control group (p=0.001 and p=0.001, respectively). At 24 h post-injection, the concentrations of IFN-gamma and IL-10 in the aqueous humor reached peak levels, and were significantly different from the control group (p=0.022 and p=0.003). The concentrations of IFN-gamma in serum at 4 and 24 hours were significantly different from the control group (p=0.033 and p=0.032). The concentration of IL-10 in serum, at 24 h post-injection, was also found to be significantly different from the control group (p=0.003). The cytokine expression levels in the aqueous humor were consistent with what would be expected during the process of inflammation.


CONCLUSIONS
Both IL-1 and IL-6 appear to play an important role in acute anterior uveitis; furthermore, the severity of inflammation may be associated with the dynamic balance of IFN-gamma and IL-10. Our results suggest that the cytokine network might be a useful therapeutic target in the treatment of acute anterior uveitis.
Xu
Yingzhi
Y
Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Chen
Wei
W
Lu
Hong
H
Hu
Xiaofeng
X
Li
Shang
S
Wang
Jing
J
Zhao
Li
L
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D013997:Time Factors; D014605:Uveitis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides
Invest Ophthalmol Vis Sci. 2003 May;44(5):2184-91
12714660
J Immunol. 1994 Nov 1;153(9):3967-78
7930605
Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2306-13
15223810
Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5450-7
18757518
Mol Vis. 2009;15:619-28
19347047
Am J Pathol. 2008 Nov;173(5):1440-54
18832572
Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1711-7
17389503
Curr Med Res Opin. 2004;20(2):155-7
15006008
Clin Immunol Immunopathol. 1997 May;83(2):117-26
9143372
Folia Biol (Praha). 2005;51(6):188-97
16419614
J Fr Ophtalmol. 2006 Feb;29(2):146-52
16523155
Cardiovasc Res. 2008 Aug 1;79(3):360-76
18487233
Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3230-8
17591893
J Immunol. 2000 Jun 1;164(11):5998-6004
10820283
Clin Exp Ophthalmol. 2001 Apr;29(2):48-51
11341445
Immunol Lett. 2001 Aug 1;78(1):41-4
11470150
Ophthalmic Res. 2001 Sep-Oct;33(5):251-5
11586057