INTERLEUKIN-1-ALPHA, INTERLEUKIN-1-BETA, AND TUMOR-NECROSIS-FACTOR GENE-EXPRESSION IN ENDOTOXIN-INDUCED UVEITIS

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 (EI U) in rats. Method. EIU was induced by lipopolysaccharide (LPS) inject ion 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) we re quantified by a semiquantitative polymerase chain reaction (PCR) me thod; 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 expres sion 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 10 0-fold) at 3 to 6 hours. A second peak (60-fold) was observed at 24 ho urs, and the expression returned to near basal levels (3-fold) at 48 h ours. Expression of IL-1 beta and TNF genes showed a pattern similar t o that of IL-1 alpha. Three hours after LPS treatment, IL-1 beta and T NF genes were found by in situ hybridization histochemistry to be expr essed by ''histiocyte-like'' cells in the stroma of the ICB. None of t hese 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 ''his tiocyte-like'' cells in the ICB, and may have an important role in EIU .