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Abstract
PURPOSE: An intertwined cascading network of cytokines is believed to direct the development of endotoxin-induced uveitis (EIU). This study investigated mRNA levels of interleukin (IL) 1 alpha, IL-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta 1, and the helper T lymphocyte marker, CD4, during the course of EIU in rats. METHODS: Reverse transcription followed by polymerase chain reaction amplification was used to determine relative mRNA levels in four ocular tissues (iris/ciliary body, cornea, lens, and neuroretina) at 0, 1, 3, 6, 24, and 48 hours after subcutaneous injection of 200 micrograms of Escherichia coli endotoxin. RESULTS: Four general patterns of mRNA expression were observed: (1) constitutively expressed and unaffected by endotoxin; (2) constitutively expressed but further induced by endotoxin, reaching peak levels at 3 hours postinjection; (3) initially undetectable or marginally detectable and induced by endotoxin, with peak levels occurring 3 hours postinjection; and (4) never present at appreciable levels. The most dramatic responses were seen in the mRNA levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma in iris/ciliary body. Lesser mRNA level responses were found for IL-1 beta and IL-6 in cornea and for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma in neuroretina. Little or no changes in mRNA levels were observed for CD4 or TGF-beta 1 in any tissue or for any mRNA examined in lens. CONCLUSIONS: These data show that subcutaneous endotoxin induces cytokine mRNA expression differentially in ocular tissues. These data support the hypothesis that induction of cytokine expression in iris/ciliary body plays a major role in the development of EIU.