ADDITIVE EFFECT OF NITRIC-OXIDE AND PROSTAGLANDIN-E(2) SYNTHESIS INHIBITORS IN ENDOTOXIN-INDUCED UVEITIS IN THE RABBIT

The involvement of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) w as investigated in a model of intraocular inflammation induced by intr avitreal injection of endotoxin (lipopolysaccharide, LPS, 10 ng) in ra bbits. The severity of uveitis, the myeloperoxidase (MPO) activity in iris-ciliary body, and the protein concentration in aqueous humor were determined. Nitric oxide synthase (NOS) and cyclooxygenase (COX) acti vities were assessed respectively by nitrite and PGE(2) levels in aque ous humor. Treatment with inhibitors of NOS (N-G-nitro-L-arginine meth yl ester, L-NAME, 50 mg/kp i.p.) or COX (diclofenac, 30 mu g, topicall y), alone or in combination, were compared to a saline-treated group. Diclofenac or L-NAME alone reduced or delayed the intensity of uveitis , and partially decreased the protein concentration in aqueous humor; diclofenac, but not L-NAME, partially reduced the polymorphonuclear le ukocyte infiltration in the iris ciliary body as indicated by the MPO activity. Treatment with both inhibitors in combination diminished the clinical uveitis, the disruption of the blood-aqueous barrier and the MPO activity in the iris-ciliary body. We conclude that NO and PGE(2) have additive effects in endotoxin-induced uveitis in rabbits, and th at the inhibition of both pathways would improve the therapeutical man agement of uveitis.