Af. Devos et al., EXPRESSION OF MULTIPLE CYTOKINES AND IL-1RA IN THE UVEA AND RETINA DURING ENDOTOXIN-INDUCED UVEITIS IN THE RAT, Investigative ophthalmology & visual science, 35(11), 1994, pp. 3873-3883
Purpose. Ample evidence is available demonstrating that cytokines play
a pivotal role in the pathogenesis of uveitis. Because little is know
n concerning the site of cytokine synthesis in the eye, cytokine mRNA
expression was analyzed in the uvea, retina, and cornea during endotox
in-induced uveitis rat. Methods. RNA was isolated from the iris, cilia
ry body, choroid-sclera, retina, and cornea at different points in tim
e after foot-pad injection of 200 mu g lipopolysaccharide (LPS) in Lew
is rats. Reverse-transcription polymerase chain reaction analysis was
used to determine tumor necrosis factor alpha (TNF-alpha), interleukin
1 beta (IL-1 beta), IL-6, IL-10, interferon gamma (IFN-gamma), monocy
te chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (M
IP-2), and IL-1 receptor antagonist (IL-1RA) mRNA expression. Results.
Maximal mRNA expression of all cytokines examined already was observe
d in the uvea 4 hours after systemic LPS injection, before the onset o
f clinical uveitis. Elevated expression of TNF-alpha, IL-1 beta, IL-6,
IFN-gamma, MCP-1, and MIP-2 was also observed concomitant with maxima
l uveitis, at 22 to 24 hours. Except for IL-10 and IFN-gamma, all cyto
kines investigated were induced in the retina, with maximal expression
at 22 to 24 hours. Expression of IL-1RA was detected in the uvea and
retina at 4 hours and remained elevated up to 48 hours, when the clini
cal uveitis started to decline. LPS did not induce cytokine expression
in the cornea. Strikingly, a considerable expression of IL-1RA was fo
und in normal corneas, suggesting an inherent control mechanism for IL
-l-mediated responses. Conclusions. Systemic LPS injection induces ele
vated mRNA expression of multiple cytokines and IL-1RA in the uvea and
retina during various stages of EIU. This suggests that these mediato
rs may contribute to the development and recovery of this intraocular
inflammation.