KINETICS OF INTRAOCULAR TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6 IN ENDOTOXIN-INDUCED UVEITIS IN THE RAT

Purpose. To determine the kinetics of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in serum and aqueous humor of rats with different susceptibilities to endotoxin-induced uveitis (EIU), after footpad in jection of lipopolysaccharide (LPS). Methods. Samples were collected f rom EIU-susceptible Lewis rats and EIU-resistant Brown Norway (BN) rat s for up to 72 hours after LPS injection. Specific bioassays were used to measure TNF and IL-6 activity. Northern blot analysis was used to assess intraocular IL-6 mRNA expression. Results. High levels of TNF a nd IL-6 were detected in serum of both rat strains early after LPS inj ection. A second rise in serum TNF was observed at 18 to 20 hours in L ewis rats only. In aqueous humor of Lewis rats, high levels of TNF and IL-6 were observed early after LPS injection (2 to 8 hours) and conco mitant with maximal uveitis (18 to 24 hours). Low levels of TNF and IL -6 were found in aqueous humor of BN rats. Ocular IL-6 mRNA was detect ed at the same time as IL-6 activity was measured in aqueous humor. Co nclusions. The results of this study indicate that both TNF and IL-6 m ay play a role in the pathogenesis of EIU. The early release of TNF in aqueous humor during EIU suggests that this cytokine may serve as an initial mediator of intraocular inflammation. Furthermore, Northern bl ot analysis indicates that IL-6 is produced locally during EIU.