The role of endogenous eicosanoids in rabbit-intraocular inflammation.
The role of endogenously released eicosanoids in intraocular inflammation was assessed in two rabbit models. The models were: (1) paracentesis in which only breakdown of blood-aqueous barrier (BAB) occurs and (2) uveitis induced by endotoxin in which the disruption of the BAB and polymorphonuclear leukocyte infiltration are the predominant events. Indomethacin (a specific cyclooxygenase inhibitor) applied topically inhibited both the disruption of the BAB and increased levels of aqueous humor 6-keto-Prostaglandin (PG)F1 alpha. However, indomethacin and flurbiprofen applied topically and BWA4C or BWA218C (both selective lipoxygenase inhibitors) given parenterally, did not inhibit BAB response in endotoxin-induced uveitis. The cyclooxygenase inhibitors attenuated PGE2 release into aqueous humor. The 5-lipoxygenase inhibitors reduced the PMN infiltration as well as LTB4 release into aqueous humor. However, myeloperoxidase activity (an index for PMN chemotaxis) in iris-ciliary body was not affected by these drugs. Furthermore, concentrations of LTB4 in aqueous humor after paracentesis and uveitis-induced by endotoxin were similar, although in the former model there was no leukocyte infiltration, but in the latter model this leukocyte response was predominant. The results of this study suggest that locally released autocoids may not initiate ocular inflammation and other mediators such as cytokines may be involved in the inflammatory responses of the rabbit eye. We tried to detect IL-1 activity in aqueous humor following endotoxin. However, we could not detect the presence of IL-1-like activity, possibly because endotoxin also releases PGs, which inhibit IL-1 bioassay.
Kulkarni
P S
PS
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Research Institute.
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D001693:Biological Transport, Active; D001769:Blood / Q000378:metabolism; D002924:Ciliary Body / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D004195:Disease Models, Animal; D004731:Endotoxins; D004926:Escherichia coli; D007375:Interleukin-1 / Q000378:metabolism; D007498:Iris / Q000201:enzymology; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D014605:Uveitis / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D007375:Interleukin-1; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D009195:Peroxidase; D015232:Dinoprostone