The subcutaneous injection of bacterial endotoxin in Lewis rats produces an acute intraocular inflammation evolving over a 24-hour period. This endotoxin-induced uveitis (EIU) is characterized by a biphasic protein exudation and a cellular infiltrate composed of macrophages and polymorphonuclear neutrophils (PMN). We used this model to study the mechanism of cellular infiltration in peripheral organs. EIU was induced with an injection of LPS (Salmonella typhimurium) at 350 fg/kg. The level of cytokine-induced neutrophil chemoattractant (CINC) was measured every two hours in the serum and in the aqueous humor of the eye. The kinetics of CINC production in the systemic circulation showed a rapid rise, peaking two hours after LPS injection, followed by a progressive decline over the following eight hours. In the eye, the CINC levels increased above the serum levels 10 hours after EIU induction, corresponding to the time of cellular infiltration. The inhibition of leukocyte infiltration by 56 and 64 percent with the antiadhesion molecule Ab 1B6 (2mg/rat) was accompanied by only a slight reduction in the aqueous humor CINC levels of nine and 16 percent respectively, indicating that the intraocular CINC was produced by ocular cells. The specific effect of CINC in the eye was confirmed when a direct intraocular injection of 250 ng of purified CINC was followed by a significant PMN infiltration, in the absence of protein exudation. The data demonstrate that the production of chemotactic factors by ocular tissue participates in the inflammatory reaction induced by peripheral LPS injection.
