CYTOKINE MESSENGER-RNA LEVELS IN RAT OCULAR-TISSUES AFTER SYSTEMIC ENDOTOXIN TREATMENT

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, transformi ng growth factor (TGF)-beta(1), and the helper T lymphocyte marker, CD 4, during the course of EIU in rats. Methods. Reverse transcription fo llowed by polymerase chain reaction amplification was used to determin e relative mRNA levels in four ocular tissues (iris/ciliary body, corn ea, lens, and neuroretina) at 0, 1, 3, 6, 24, and 48 hours after subcu taneous injection of 200 mu g of Escherichia coli endotoxin. Results. Four general patterns of mRNA expression were observed: (1) constituti vely expressed and unaffected by endotoxin; (2) constitutively express ed but further induced by endotoxin, reaching peak levels at 3 hours p ostinjection; (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 respo nses 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 of no chan ges in mRNA levels T were observed for CD4 or TGF-beta(1) in any tissu e 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 o f cytokine expression in iris/ciliary body plays a major role in the d evelopment of EIU.