Nitric oxide and transforming growth factor-beta levels during experimental uveitis in the rabbit.

OBJECTIVE To determine changes in the levels of nitric oxide metabolites and transforming growth factor-beta (TGF-beta) in the rabbit aqueous humour during ocular inflammation. DESIGN Active experimental uveitis was induced by injection of porcine lens protein (PLP) in three rabbits 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 immunosorbent 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 modification 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 < or = 0.005) (432 nmol/mL for the PLP group and 112 nmol/mL for the HSA group) and a significant decrease (p < or = 0.03) in the mean TGF-beta level (3.1 ng/mL and 0.3 ng/mL respectively). CONCLUSIONS Nitric oxide may be used as a marker for intraocular inflammation. The increased production of nitric oxide may reflect the loss of immunologic privilege of the ocular microenvironment that occurs during inflammation.