Endotoxin-induced uveitis in the rat

Forrester, John V.; Worgul, Basil V.; Merriam, George R.

doi:10.1007/bf00417543

Cited by 65 publications

(27 citation statements)

References 22 publications

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“…Fifty micrograms of LPS diluted in 10 l of sterile saline solution was injected 24 h before treatment in animals treated with multiple drug doses. The higher LPS dose was administered to maintain intraocular inflammation over the treatment period (8). LPS was injected through the sclera into the vitreous using a 30.5-gauge needle connected to a Hamilton syringe.…”

Section: Animalsmentioning

confidence: 99%

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Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

Goldblum¹,

Rohrer²,

Frueh³

et al. 2002

Antimicrob Agents Chemother

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Little is known about the ocular penetration of amphotericin B (AMB) and its lipid formulations, the current drug of choice in fungal endophthalmitis. The ocular distribution of AMB lipid complex (ABLC), liposomal AMB (L-AMB), and AMB deoxycholate (D-AMB) was studied in a rabbit model. D-AMB (1 mg/kg of body weight/day), ABLC (5 mg/kg/day), or L-AMB (5 mg/kg/day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 consecutive days after induction of unilateral uveitis by intravitreal injection of endotoxin. AMB concentrations in aqueous humor, vitreous humor, and plasma were determined by high-pressure liquid chromatography 16 h after administration of a single dose or 24 h after the last of seven doses. After single-dose administration, L-AMB achieved at least eightfold-higher AMB concentrations in the aqueous of inflamed eyes than ABLC or D-AMB (1.21 ؎ 0.58 g/ml versus 0.14 ؎ 0.04 and 0.11 ؎ 0.09 g/ml, respectively). At that time point no drug was detectable in the vitreous. After 7 days of treatment, the concentration of AMB in the vitreous was higher after treatment with L-AMB (0.47 ؎ 0.21 g/ml) than after treatment with ABLC (0.27 ؎ 0.18 g/ml) and D-AMB (0.16 ؎ 0.04 g/ml). Similarly, AMB concentration in the aqueous was higher after repeated doses of L-AMB (0.73 ؎ 0.43 g/ml) than after repeated doses of ABLC (0.03 ؎ 0.02 g/ml) or D-AMB (0.13 ؎ 0.06 g/ml). No AMB was detected in noninflamed eyes. Following systemic administration, AMB distribution to the eye is inflammation dependent and occurs sequentially, first to the aqueous and then to the vitreous. Compared to D-AMB and ABLC, L-AMB reaches higher drug concentrations in both ocular compartments.Fungal endophthalmitis is a sight-threatening infection that is often difficult to treat. Intravenous amphotericin B (AMB), with or without additional 5-flucytosine, is considered the treatment of choice for severe systemic fungal infections and is often used as adjuvant treatment for intraocular infections caused by a wide range of fungi (24). The usefulness of this polyene, however, is limited by a number of adverse reactions (26), particularly its dose-limiting nephrotoxicity (12, 23). Renal insufficiency in association with azotemia, renal tubular acidosis, and impaired urinary concentrating capacity resulting in electrolyte imbalance often leads to dose reduction or premature discontinuation of the drug (5, 10). The lipid formulations of AMB now available for clinical use may offer therapeutic advantages. Due to their reduced nephrotoxicity and different pharmacodynamic properties, higher doses of the parent compound may be delivered to infected tissues (3, 17, 29).The exact mechanism responsible for the reduced toxicity of the lipid formulations is not yet known. A recent publication suggests that it may be related to lower concentrations of free AMB found in plasma after administration of lipid-associated AMB. The exposure to free and protein-bound AMB in subjects treated with liposomal AMB (L-AMB) was found to be approximat...

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Section: Animalsmentioning

confidence: 99%

“…Single-dose kinetics of L-AMB (AmBisome; NeXstar Pharmaceuticals) were studied over 24 h. One hour after induction of uveitis, 15 rabbits were given 5-mg/kg L-AMB at 2 mg/ml over 10 min by steady bolus injection into an ear vein. Three to five animals per time point were sacrificed at 4,8,16, and 24 h after drug administration.…”

Section: Animalsmentioning

confidence: 99%

Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

Goldblum¹,

Rohrer²,

Frueh³

et al. 2002

Antimicrob Agents Chemother

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“…EIU in various kinds of animals has been established as an experimental model for human uveitis associated with gram-negative bacterial infection, such as ankylosing spondylitis, acute anterior uveitis and Reiter's syndrome. A clinical feature of EIU is an increase in systemic vascular permeability under an upregulation of major histocompatibility complex class II antigen expression on ocular tissue (Forrester et al 1980;Rosenbaum et al 1980). This report describes a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia.…”

mentioning

confidence: 92%

“…1999: 77: 110-113 Copyright C Acta Ophthalmol Scand 1999. ISSN 1395-3907 I t is described that systemic or local injection of endotoxin, the lipopolysaccharide (LPS) constituents of gram-negative bacterial outer membranes, will induce inflammation in several organs including eyes (Forrester et al 1980;Rosenbaum et al 1980). This inflammatory process characterized by an acute anterior uveitis is described as endotoxininduced uveitis (EIU).…”

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confidence: 99%

Antibiotic‐induced endotoxemia in a patient with endogenous endophthalmitis

Yamada

Aida

Kakimoto

et al. 1999

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: The aim of the study is to describe a case of suspected endotoxininduced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia. Methods: The human leukocyte antigen (HLA) typing of peripheral leukocytes was studied by lymphocytotoxicity technique. Histological and immunohistochemical studies of paraffin embedded specimen were conducted. Results: Findings of HLA typing revealed positive reaction for B 51, Cw 3, DR 8, DR 11, DQ 3. The vitreous body of an eviscerated eye was occupied by the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and Sudan black staining positive foamy cells, including melaniferous phagocytes, identified as CD 68 positive macrophage. Conclusion: It is suggested that antibiotic-induced endotoxemia of a patient with septic endogenous endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA and endotoxin activated macrophages may release cytokines, followed by fibrin formation and subsequent granuloma.Key words: Penicillin-binding proteins -endotoxemia -imipenem/cilastatin -septic endogenous endophthalmitis -liver abscess -endotoxin-induced uveitis -intravitreal granuloma.Acta Ophthalmol. Scand. 1999: 77: 110-113 Copyright C Acta Ophthalmol Scand 1999. ISSN 1395-3907 I t is described that systemic or local injection of endotoxin, the lipopolysaccharide (LPS) constituents of gram-negative bacterial outer membranes, will induce inflammation in several organs including eyes (Forrester et al. 1980;Rosenbaum et al. 1980). This inflammatory process characterized by an acute anterior uveitis is described as endotoxininduced uveitis (EIU). EIU in various kinds of animals has been established as an experimental model for human uveitis associated with gram-negative bacterial infection, such as ankylosing spondylitis, acute anterior uveitis and Reiter's syndrome. A clinical feature of EIU is an increase in systemic vascular permeability under an upregulation of major histocompatibility complex class II antigen expression on ocular tissue (Forrester et al. 1980;Rosenbaum et al. 1980). This report describes a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia. Case reportA 68-year-old woman was admitted because of an acute endogenous endophthalmitis on the day of the initial observation, although 9 days after the onset.Visual acuity was CF at 1 ft in her right eye, and 0.6 (1.2 Xπ0.75 DΩcyl-1.50 D180ae) in the left. Ocular sonographic examinations revealed shallow anterior chamber, vitreous opacity, abnormal shadow around the optic nerve, intraorbital opacification and thickening of the posterior eyeball, however, no signs of the intraocular and orbital shadow of a foreign body or tumor were detected. A CT scan showed thickening of left cornea, globe wall and extraocular muscles, and inflammatory changes, such as opacities of intraorbital lipids. Laboratory data showed an increase of serum transaminases, g-g...

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“…Endotoxin-induced uveitis (EIU) is a well-established experimental model for acute intraocular inflammation [1,2]. EIU has been beneficial in studying inflammatory mechanisms of uveitis and for evaluating potential treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Effects of a New Immunotherapeutic Agent (CG5601) on Endotoxin-Induced Uveitis

et al. 2003

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CG5601 is a novel immunomodulatory substance showing anti-inflammatory properties comparable to thalidomide. To investigate the anti-inflammatory effects of CG5601 in endotoxin-induced uveitis (EIU) and to evaluate its influence on leukocyte-endothelium interaction, the anterior chamber inflammatory reaction was assessed and intravital fluorescence microscopy was carried out at 2, 4, 8 and 24 h. Lewis rats received an intraperitoneal injection of CG5601 (200 mg/kg b.w.) at the time of lipopolysaccharide injection. At 8 and 24 h, CG5601 inhibited the cell migration and protein concentration in the aqueous humor compared to untreated EIU (p < 0.0001). There was no significant difference between nontreated animals and vehicle controls. The treatment of CG5601 reduced the number of rolling leukocytes. At early time points (2 and 4 h), inhibition of rolling leukocyte flux was significant (p < 0.005). The rise of serum TNF-α levels in EIU at 2 h was reduced. CG5601 exerts potent anti-inflammatory effects in EIU.

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Endotoxin-induced uveitis in the rat

Cited by 65 publications

References 22 publications

Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

Antibiotic‐induced endotoxemia in a patient with endogenous endophthalmitis

Effects of a New Immunotherapeutic Agent (CG5601) on Endotoxin-Induced Uveitis

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