Effects of steroids and immunosuppressive drugs on endotoxin-uveitis in rabbits.
Anti-inflammatory actions of dexamethasone (DEXA), Cyclosporin A (CSA) and Rapamycin (RAPA) were assessed on uveitis induced by intravitreal E-coli Endotoxin (100ng) in rabbits at 24 hrs. In this model, endotoxin caused a breakdown of the blood-aqueous barrier (BAB) and polymorphonuclear neutrophils (PMN) infiltration into the aqueous humor (AH) and iris-ciliary body (ICB). Intramuscular (I.M.) DEXA (2mg/kg) but not topical DEXA (0.1% 6 x daily) inhibited AH leukocytes and protein level. However, both routes caused an inhibition of AH Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4). In the ICB, I.M. DEXA significantly inhibited PGE2 synthesis and myeloperoxidase (MPO) activity. I.M. CSA (25mg/kg) and I.M. RAPA (10mg/kg) inhibited the AH leukocytes and protein content and MPO activity in the ICB. RAPA also inhibited AH protein and eicosanoid (except AH LTB4) levels in both the AH and ICB. Interestingly, castor oil, a vehicle of CSA, also inhibited AH leukocytes and the release of PGE2 into AH and from ICB. In summary, systemic administration of DEXA and other immunosuppressive drugs CSA and RAPA significantly inhibited endotoxin-induced uveitis in rabbits.
Ohia
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EO
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky.
Mancino
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Kulkarni
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D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002924:Ciliary Body / Q000201:enzymology / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007498:Iris / Q000201:enzymology / Q000473:pathology; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011090:Polyenes / Q000627:therapeutic use*; D011817:Rabbits; D020123:Sirolimus; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D004731:Endotoxins; D007166:Immunosuppressive Agents; D011090:Polyenes; D007975:Leukotriene B4; C044101:endotoxin, Escherichia coli; D003907:Dexamethasone; D016572:Cyclosporine; D009195:Peroxidase; D015232:Dinoprostone; D020123:Sirolimus