NITRIC-OXIDE AND TRANSFORMING GROWTH-FACTOR-BETA LEVELS DURING EXPERIMENTAL UVEITIS IN THE RABBIT

Objective: To determine changes in the levels of nitric oxide metaboli tes and transforming growth factor-beta (TGF-beta) in the rabbit aqueo us humour during ocular inflammation. Design: Active experimental uvei tis was induced by injection of porcine lens protein (PLP) in three ra bbits and of human serum albumin (HSA) in three rabbits; three control rabbits received an injection of saline. Outcome measures: Degree of inflammation, antibody titres (determined with the enzyme-linked immun osorbent assay), and aqueous humour levels of nitric oxide metabolites and TGF-beta. A modified Griess assay for nitrites and nitrates (NO2- and NO3-) was used as a measure of nitric oxide generation, and a mod ification of the CCL-64 mink lung epithelial cell bioassay was used to quantify TGF-beta levels. Results: Following the primary immunologic challenge both experimental groups initially showed a two- to fourfold increment in aqueous levels of nitric oxide metabolites and TGF-beta compared with baseline values. At the peak of the clinically observed inflammation there was a significant increase in the mean nitric oxide metabolite level compared with the control value (p less than or equa l to 0.005) (432 nmol/mL for the PLP group and 112 nmol/mL for the HSA group) and a significant decrease (p less than or equal to 0.03) in t he mean TGF-beta level (3.1 ng/mL and 0.3 ng/mL respectively). Conclus ions: Nitric oxide may be used as a marker for intraocular inflammatio n. The increased production of nitric oxide may reflect the loss of im munologic privilege of the ocular microenvironment that occurs during inflammation.