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Abstract
PURPOSE: To localize and determine the levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and tumor necrosis factor (TNF) gene expression in the process of endotoxin-induced uveitis (EIU) in rats. METHOD: EIU was induced by lipopolysaccharide (LPS) injection in male Lewis rats weighing 150 to 200 g. The levels of IL-1 alpha, IL-1 beta, and TNF gene expression in the iris-ciliary body (ICB) were quantified by a semiquantitative polymerase chain reaction (PCR) method; in situ hybridization histochemistry was carried out to localize the gene transcripts. RESULTS: Little expression of IL-1 alpha, IL-1 beta, and TNF genes was observed in normal ICB. IL-1 alpha gene expression began to increase (about 10-fold greater than that of the control) as early as 1 hour after the LPS treatment, reached a peak (about 100-fold) at 3 to 6 hours. A second peak (60-fold) was observed at 24 hours, and the expression returned to near basal levels (3-fold) at 48 hours. Expression of IL-1 beta and TNF genes showed a pattern similar to that of IL-1 alpha. Three hours after LPS treatment, IL-1 beta and TNF genes were found by in situ hybridization histochemistry to be expressed by "histiocyte-like" cells in the stroma of the ICB. None of these genes were detected in the control rats. CONCLUSIONS: Expression of IL-1 alpha, IL-1 beta, and TNF genes was dramatically up-regulated in the process of EIU. These genes were found to be expressed in "histiocyte-like" cells in the ICB, and may have an important role in EIU.