title: Immunopharmacological analysis of endotoxin-induced uveitis in the rat.
abstract: Footpad injection of endotoxin causes exclusive ocular inflammation in the rat. In order to clarify its physiopathologic mechanism, we studied the effect of different treatments on endotoxin-induced uveitis (EIU). Salmonella endotoxin was injected into the footpads of Lewis rats. 18 hr later, inflammation was assessed by evaluating proteins and cells in the anterior chamber; arachidonic acid (AA) metabolites, prostaglandin E2 and leukotriene B4, as well as substance P were measured by radioimmunoassay, and Ia-(MHC class II)-antigen expression in ciliary body was assessed by immunohistochemistry. The effect of inhibitors of phospholipase A2 (EPC), of lipoxygenase (azelastine) and of cyclo-oxygenase (diclofenac), as well as dexamethasone, cyclosporine (CsA) and anti-Ia antibody, were evaluated on these parameters. Phospholipase A2 inhibitor EPC and dexamethasone were most effective on inflammation: they also reduced AA metabolites very effectively and prevented Ia-expression. Lipoxygenase and cyclo-oxygenase inhibitors were partially effective on inflammation and on AA metabolites but failed to prevent Ia-expression. Immunosuppressive treatments (CsA and anti-Ia-antibody) also reduced inflammation. Our findings suggest that inflammation mediators initiate inflammation in EIU. Ia-Ag-expression is secondarily produced by mediators leading to additional inflammation due to immune mediated mechanisms.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Japan.
authors.forename: C P
authors.initials: CP
authors.lastname: Herbort
authors.forename: A
authors.initials: A
authors.lastname: Okumura
authors.forename: M
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000032:analysis / Q000276:immunology; D002924:Ciliary Body / Q000276:immunology; D015232:Dinoprostone / Q000032:analysis; D004731:Endotoxins; D005136:Eye Proteins / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012475:Salmonella; D014605:Uveitis / Q000209:etiology* / Q000276:immunology
chemical_list: D004731:Endotoxins; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; D007975:Leukotriene B4; D015232:Dinoprostone