Effects of experimental ocular inflammation on ocular immune privilege.

PURPOSE: To determine whether the inflammation of endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) alters key in vivo and in vitro parameters of ocular immune privilege. METHODS: For EIU induction, C3H/HeN mice received 200 microg lipopolysaccharide (LPS). For EAU induction, B10.A mice were immunized with 50 microg interphotoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell proliferation. Eyes with EAU were assessed for the capacity to support anterior chamber (AC)-associated immune deviation (ACAID) induction after injection of ovalbumin (OVA). RESULTS: Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH promptly lost its capacity to suppress T-cell proliferation and became mitogenic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 days and continued to remain elevated thereafter. Whereas 11-day EAU AqH failed to suppress T-cell proliferation, AqH at later time points reacquired immunosuppressive properties. Injection of OVA into the AC of eyes of mice with EAU failed to induce ACAID. CONCLUSIONS: The intraocular inflammation of EIU and EAU disrupted important parameters of immune privilege, ranging from breakdown of the blood- ocular barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate immune expression and inflammation can be a property even of inflamed eyes.     

Recurrent intraocular inflammation in endotoxin-induced uveitis

PURPOSE: Endotoxin-induced uveitis (EIU) in rats and mice peaks 24 hours after endotoxin injection and is commonly assumed to be a monophasic disease. This study examined intraocular inflammation at later time points to determine whether endotoxin injection can induce recurrent intraocular inflammation in strains of mice with high or moderate levels of susceptibility to EIU. METHODS: EIU was elicited in two mouse strains with high (C3H/HeN) and moderate (FVB/N) susceptibility, by means of intraperitoneal injections of Salmonella typhimurium endotoxin. Inflammatory cells in the anterior and posterior segments of the eye were counted by a masked observer on histologic sections of eyes from 1 to 17 days after endotoxin injection. RESULTS: A bimodal distribution of inflammatory cell infiltration was noted in eyes from C3H/HeN mice. As previously reported, inflammation peaked at 24 hours after endotoxin injection. However, a second, more pronounced peak of intraocular inflammation occurred approximately 5 days after endotoxin injection. FVB/N mice had a single peak of intraocular inflammation 4 days after injection. CONCLUSIONS: Endotoxin injection in C3H/HeN elicits recurrent intraocular inflammation. The previously unrecognized second peak of inflammation is more severe than the initial inflammatory disease. Studies on this second inflammatory peak may be useful in determining the pathogenesis of recurrent uveitis in humans.     

A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor

Purpose

Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU)

Methods

EIU was induced in female Lewis rats by single footpad injections of 200 µg of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients.

Results

Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region.

Conclusions

TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.     

地塞米鬆緩釋顆粒在糖尿病性白内障手術中的應用

目的 研究Tenon’s囊下植入地塞米松缓释颗粒控制糖尿病性白内障术后前房炎症反应的有效性和安全性。方法双眼糖尿病性白内障患者37例(74眼),一眼仅于白内障术毕Tenon’s囊下植入地塞米松缓释颗粒,术后不再使用激素性眼液,作为实验组;另一眼不植入地塞米松缓释颗粒,术后常规滴典必舒眼液,作为对照组。分别观察术后1、3、7、15天的前房炎症反应、睫状充血、眼压、角膜上皮、伤口愈合状况及血糖水平等指标。结果 术后1、15天时,两组的前房炎症反应无显著性差异;术后3、7天,实验组较对照组前房炎症反应轻(P<0.05);术后1、3、7、15天,两组睫状充血评分无显著差异;两组术后各天眼压无显著性差异;地塞米松缓释颗粒对血糖、角膜上皮及伤口愈合状况无明显影响。结论 对合并糖尿病的白内障患者,术毕Tenon’s囊下植入地塞米松缓释颗粒是一种安全有效的控制术后前房炎症反应的方式。     

Randomized clinical trial of a new dexamethasone delivery system (surodex) for treatment of post-cataract surgery inflammation

ObjectiveTo evaluate the safety of Surodex Drug Delivery System (Oculex Pharmaceuticals, Inc., Sunnyvale, CA) containing dexamethasone 60 μg, for use in cataract surgery, and to compare its anti-inflammatory efficacy with conventional dexamethasone 0.1% eyedrops.DesignRandomized, masked, and partially controlled trial.ParticipantsSixty eyes of 60 Asian patients undergoing extracapsular cataract extraction with intraocular lens implantation were examined. Of these, 28 eyes of 28 patients served as control eyes. Patients were stratified for age and presence of diabetes mellitus.InterventionSurodex was inserted in the anterior chamber of 32 eyes at the conclusion of surgery. These eyes received placebo eyedrops four times a day after surgery for 4 weeks. Control eyes received neither Surodex nor a placebo implant but were prescribed conventional 0.1% dexamethasone eyedrops four times a day for 4 weeks.Main outcome measuresAnterior chamber cells and flare were clinically graded at the slit lamp. Anterior chamber flare was objectively assessed with the Kowa FM500 Laser Flare Meter (Kowa Co. Ltd, Tokyo, Japan) for up to 3 months after surgery. Intraocular pressure and corneal endothelial specular microscopy with morphometric cell analysis were performed for up to 1 year after surgery.ResultsClinical slit-lamp assessment of anterior chamber flare and cells showed no difference between Surodex-treated eyes and dexamethasone eyedrop-treated eyes. Flare meter readings showed lower flare levels in the Surodex group at all postoperative visits compared with the dexamethasone eyedrop group. Flare reduction in the Surodex group reached statistical significance at days 4, 8, 15, and 30 after surgery. At 3 months, flare was reduced to preoperative levels in the Surodex group but was still raised in the dexamethasone eyedrop group. Five eyes in the dexamethasone eyedrop group required augmentation of steroids and were deemed therapeutic failures as opposed to one eye in the Surodex group. One patient in the dexamethasone eyedrop group developed postoperative open-angle glaucoma with profound visual field loss and optic disc cupping, resulting in hand movements vision. No significant difference in endothelial cell loss was noted between Surodex-inserted eyes and dexamethasone eyedrop-treated eyes for up to 1 year after surgery.ConclusionsIntraocular placement of a single Surodex is a safe and effective treatment method to reduce intraocular inflammation after cataract surgery. There was no statistical difference in efficacy between Surodex and 0.1% dexamethasone eyedrops in reducing intraocular inflammation, as measured by clinical methods, while Surodex was clearly superior to eyedrops in reducing aqueous flare as objectively assessed with the laser flare meter.     

Interleukin 10 inhibits inflammatory cells infiltration in endotoxin-induced uveitis

Background: Endotoxin-induced uveitis (EIU) is a model for acute anterior uveitis associated with a variety of pro-inflammatory cytokines and nitric oxide production. Interleukin 10 (IL-10) down-regulates these inflammatory mediators. We report a study of the effect of systemic administration of IL-10 on the inflammatory parameters of EIU. Methods: Uveitis was induced in C3H/HeN mice by subcutaneous injection of 200 g lipopolysaccharide (LPS) per mouse. Intraocular inflammation was assessed by leukocyte count and measurement of the protein concentration in the aqueous humor (AH). Mouse recombinant IL-10 at 1000 U or its vehicle alone were administered by three intravenous injections given 4.0 h and 0.5 h before and 8.0 h after LPS injection. Results: The inflammatory cell infiltration in the eyes was significantly reduced in four of five experiments from 40% to 64% in the groups treated with IL-10 compared to the control groups (P<0.05). In contrast, the level of protein exudation in the anterior chamber (AC) was not significantly affected by IL-10 treatment. Conclusion: IL-10 reduces the cellular infiltration in the ocular inflammation produced by endotoxin. This result suggests potential usefulness for IL-10 in the treatment of severe anterior uveitis with a strong cellular component.     

Results of intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in non-infectious posterior uveitis

AIM:To evaluate the safety and efficacy of dexamethasone implant in patients with non-infectious posterior uveitis withcystoid macular edema (CME).METHODS:Retrospective analysis of patients reports with CME secondary to non-infectious uveitis treated with dexamethasone implant. Data included type of posterior uveitis, any systemic immunosuppressive therapy, Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography (OCT) and signs of intraocular inflammation at baseline and then at 2wk postoperatively and monthly thereafter. Follow-up is up to 10mo. Any per-operative and post-operative complications were recorded.RESULTS:Six eyes of 4 patients with CME due to non-infectious posterior uveitis treated with dexamethasone implant. Diagnosis included idiopathic panuveitis, birdshot chorioretinopathy and idiopathic intermediate uveitis. At baseline mean ETDRS BCVA was 63 letters and mean CMT 556 μm at 2wk postoperatively mean ETDRS BCVA improved to 70 letters and mean CMT decreased to 329 μm. All eyes showed clinical evidence of decreased inflammation. The duration of effect of the implant was 5 to 6mo and retreatment was required in 2 eyes. Two patients required antiglaucoma therapy for increased intraocular pressures.CONCLUSION: In patients with non-infectious posterior uveitis dexamethasone implant can be a short-term effective treatment option for controlling intraocular inflammation.     

Randomized clinical trial of surodex steroid drug delivery system for cataract surgery: Anterior versus posterior placement of two surodex in the eye

OBJECTIVE: To evaluate safety and antiinflammatory efficacy of placing two Surodex (Oculex Pharmaceuticals, Inc., Sunnyvale, CA) in the eye after cataract surgery in comparison with steroid eyedrops and to compare anterior versus posterior chamber placement. DESIGN: Randomized, masked, controlled trial. PARTICIPANTS: One hundred four eyes of 104 Asian patients undergoing extracapsular cataract extraction with intraocular lens implantation were examined. Of these, 33 eyes of 33 patients served as control eyes (group A). INTERVENTION: Two Surodex pellets were inserted in the anterior chamber (AC) of 35 eyes (group B), and two Surodex pellets were inserted in the ciliary sulcus of 36 eyes (group C) at the conclusion of surgery. Control eyes received neither Surodex nor a placebo implant, but were prescribed conventional 0.1% dexamethasone eyedrops four times daily for 4 weeks. MAIN OUTCOME MEASURES: Anterior chamber flare and cells were graded clinically at the slit lamp. Anterior chamber flare was assessed objectively with the Kowa FC500 Laser Flare Meter (Kowa Co. Ltd, Tokyo, Japan). Intraocular pressure and corneal endothelial specular microscopy with morphometric cell analysis were performed for up to 1 year after surgery. RESULTS: Lower flare meter readings occurred in both Surodex groups at all postoperative visits, as compared with the dexamethasone eyedrop group, with statistical significance at days 4 (P = 0.001), 8 (P = 0.001), and 15 (P = 0.02). No difference in flare occurred between AC and ciliary sulcus placement. Clinical slit-lamp assessment of anterior chamber flare and cells showed no difference between Surodex-treated eyes and dexamethasone-treated eyes. Nine of 33 eyes (27.3%) in group A required steroid augmentation, as opposed to 4 of 71 eyes (5.6%) in groups B and C. Inflammatory symptoms were reduced in the Surodex-treated eyes, with statistical significance for ocular discomfort (P = 0.001), photophobia (P = 0.04), and lacrimation (P = 0.01). No complications occurred with Surodex-treated eyes, and no significant difference in endothelial cell loss was noted between Surodex-treated eyes and dexamethasone-treated eyes up to 1 year after surgery. CONCLUSIONS: Intraocular placement of two Surodex is a safe and effective treatment method to reduce intraocular inflammation after cataract surgery and clearly is superior to eyedrops in reducing inflammatory symptoms and aqueous flare as measured with the laser flare meter. No difference in efficacy between AC placement and ciliary sulcus placement of Surodex was detected in this study.     

龙胆泻肝汤对大鼠实验性自身免疫性葡萄膜炎的治疗作用

目的　探讨龙胆泻肝汤对大鼠实验性自身免疫性葡萄膜炎（ｅｘｐｅｒｉｍｅｎｔａｌａｕｔｏ-ｉｍｍｕｎｅｕｖｅｉｔｉｓ,ＥＡＵ）的治疗作用。方法　Ｌｅｗｉｓ大鼠随机分为对照组６只、ＥＡＵ组１８只和ＬＸＴ组１８只,光感受器间维生素Ａ结合蛋白免疫ＥＡＵ组和ＬＸＴ组大鼠。观察大鼠生理特征及眼部炎症变化,出现葡萄膜炎症时给予ＬＸＴ组大鼠龙胆泻肝汤灌胃;免疫后１２ｄ比较各组大鼠眼组织病理学差异;免疫后每隔４ｄ检测房水蛋白及血清中白蛋白、球蛋白变化。结果　成功制备了ＥＡＵ大鼠模型;免疫后５ｄ大鼠开始出现葡萄膜炎症状,１２ｄ炎症最重。ＥＡＵ大鼠肛温在１ｄ、７ｄ、１０ｄ和１２ｄ高于对照组（Ｐ＝０．０２０、０．０００、０.０１５、０．００１）;免疫后１２ｄ,ＥＡＵ组房水蛋白浓度为（３６．０３±３．２３）ｇ?Ｌ－１,ＬＸＴ组为（２４．６７±２．６０）ｇ?Ｌ－１,差异有显著统计学意义（Ｐ＝０．０００）;组织病理学显示ＥＡＵ组视网膜结构破坏程度明显高于ＬＸＴ组（Ｐ＝０．０００）。ＥＡＵ组免疫后４ｄ、８ｄ及１２ｄ白蛋白均低于对照组（Ｐ＝０．０４５、０．０００、０.０３３）,ＬＸＴ组４ｄ和８ｄ白蛋白低于正常（Ｐ＝０.０４５、０．００５）,但１２ｄ时恢复至正常;１２ｄ时ＥＡＵ组球蛋白明显高于正常（Ｐ＝０．０４７）,ＬＸＴ组未见明显异常。结论　龙胆泻肝汤能有效减轻ＥＡＵ大鼠前房炎症,减少炎症细胞浸润,保护眼部组织结构,增强机体抗氧化能力,调节免疫状态,对ＥＡＵ发挥治疗作用。     

Anti-inflammatory effect of angiotensin type 1 receptor antagonist on endotoxin-induced uveitis in rats

Background Angiotensin II type 1 (AT1) receptor-antagonists are widely used for treatment of hypertension. Recent studies have demonstrated a protective effect of renin angiotensin system (RAS) antagonism against immune-mediated inflammatory diseases such as myocarditis, chronic allograft rejection, antiglomerular basement membrane nephritis, colitis, and arthritis. However, only a few reports have demonstrated the effect of RAS in ocular inflammatory conditions. The purpose of this study was to investigate the anti-inflammatory effect of a selective AT1 receptor antagonist, losartan, on endotoxin-induced uveitis (EIU) and compare the effect on experimental autoimmune uveoretinitis (EAU). Methods To induce EIU, 7-week-old Lewis rats were injected subcutaneously with 200 μg lipopolysaccharide (LPS). Losartan was administered intravenously at the same time. The aqueous humor was collected from eyes 24 h after LPS injection. The number of infiltrating cells, protein concentration, and levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor were determined. The collected eyes were immunohistochemically stained with monoclonal antibody for activated nuclear factor (NF)-κB. To induce EAU, C57BL/6 mice (6–8 weeks old) were immunized with human interphotoreceptor retinoid binding protein (hIRBP)-derived peptide emulsified in complete Freund’s adjuvant (CFA) and concomitantly injected with purified Bordetella pertussis toxin (PTX). Clinical severity of EAU and T cell proliferative response were analyzed. Results Losartan significantly suppressed the development of EIU. Numbers of aqueous cells of control EIU rats, those from EIU rats treated with 1 or 10 mg/kg of losratan were 75.3 ± 45.6 × 10⁵, 27.9 ± 8.1 × 10⁵, or 41.3 ± 30.9 × 10⁵ cells/ml respectively (p < 0.01 vs control). Aqueous protein, TNF-α, and MCP-1 levels were also significantly decreased in a manner dependent on the amount of losartan administered (p < 0.01). Treatment of EIU rats with losartan suppressed activation of NF-κB at the iris ciliary body. Thus, the suppressive effect of losartan on ocular inflammation in EIU appeared to result from down-regulation of NF-κB activation and reduction of inflammatory cytokine production. On the other hand, in the EAU model, neither the clinical score nor the antigen-specific T cell proliferative response was significantly influenced by the treatment with losartan. Conclusions The present findings indicate that RAS may be involved in the acute inflammation of the eye, but not in T cell-dependent ocular autoimmunity. Antagonism of the RAS may be a potential prophylactic strategy for treatment of the human acute ocular inflammation.     

Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet Uveitis

Purpose

To assess the usefulness of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet disease.

Methods

The study comprised 47 healthy individuals, 78 Behçet patients without ocular involvement, 54 Behçet patients with a uveitis attack and 53 Behçet patients with uveitis in clinical remission. A single observer assigned clinical scores to anterior chamber cells, vitreous haze, and fundus lesions in the attack group. Laser flare-cell photometry measurements were performed by another observer who was masked to the clinical findings. Fundus fluorescein angiography was performed only in the remission group, and fluorescein leakage was scored by a masked retina specialist. The risk of recurrent uveitis attack was analyzed in eyes with high versus low flare values in the remission group. Main outcome measures were anterior chamber flare in Behçet patients compared to the control group, and correlations of flare with clinical scores of intraocular inflammation and with fluorescein leakage. Mann-Whitney U-test, Spearman’s bivariate correlation test, linear regression method, and Kaplan-Meier method were used for statistical analyses.

Results

Mean flare was not increased in Behçet patients without ocular involvement. It was significantly higher in patients with Behçet uveitis both during attacks and in remission (P?6 photons/msec than in eyes with flare values ≤6 photons/msec (right eyes, P?P?=?0.0184).

Conclusions

Laser flare-cell photometry is a useful objective method in the quantitative assessment of intraocular inflammation in patients with Behçet uveitis. The use of this quantitative technique in clinical trials of Behçet uveitis may provide comparable data, as it gives an objective measure of intraocular inflammation. In clinical practice, it may reduce the need for fluorescein angiography because it seems to be especially useful in monitoring persistent retinal vascular leakage in patients who are clinically in remission.

     

Effects of leukotriene B4 receptor antagonist on experimental autoimmune uveoretinitis in rats

PURPOSE: We evaluated the potential of leukotriene B4 receptor antagonist (LTB4 RA) as an anti-inflammatory agent on experimental autoimmune uveoretinitis (EAU). MATERIALS AND METHODS: LTB4 RA was administered to Lewis rats twice a day on days 0-10, 0-5, and 6-10 after immunization. Rats treated on days 0-10 after immunization were subdivided into three groups according to the dosage of LTB4 RA. The eyes were examined histopathologically, and the expression of CD 45 RC in CD 4+T cells was analyzed. RESULTS: The inflammatory changes in the eyes of EAU were decreased in all groups treated with LTB4 RA in a dose-dependent manner. The treatment with LTB4 RA on days 0-10 after immunization achieved much higher uveitis suppression. The infiltration into eye tissues by neutrophils and lymphocytes was decreased by treatment with LTB4 RA. In treated groups, the CD 45 RChigh subset decreased in the induction phase of EAU as compared with the untreated group. CONCLUSION: The suppressive mechanisms of LTB4 RA on EAU may be dependent on suppression of the activation of neutrophils and CD 4+T cells.     

Effects of topical prostaglandin analogues on the aqueous flare intensity in rabbit eyes at an early phase of endotoxin-induced uveitis

PURPOSE: We examined the effects of prostaglandin analogues on the blood-aqueous barrier(BAB) permeability in rabbit eyes at an early phase of endotoxin-induced uveitis(EIU). SUBJECTS AND METHODS: One drop of 0.005% latanoprost or 0.12% unoprostone were applied to rabbit eyes. Escherichia coli lipopolysaccharides were injected to induce uveitis. The changes in flare intensity in normal eyes and EIU eyes after application of eye drops were evaluated. The effect of cyclooxygenase inhibitor on the flare intensity changes caused by the application of unoprostone was also examined. RESULTS: Flare intensity increased significantly after a single instillation of unoprostone, and the increase was not prevented by pretreatment with cyclooxygenase inhibitor. In eyes with EIU, unoprostone caused an additional increase of flare intensity to uveitis induced flare change. Latanoprost had no effects on BAB in eyes with normal and with uveitic conditions. CONCLUSION: Latanoprost and unoprostone did not cause an excessive inflammatory reaction in rabbit eyes at an early phase of EIU.     

The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats

Background: Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation, produced by footpad injection of endotoxin (lipopolysaccharide, LPS) to mimic the human disease of acute anterior uveitis, that is useful for testing new anti-inflammatory therapy. The purpose of this study was to test the anti-inflammatory effect on EIU of thalidomide and one of its derivatives, supidimide. Methods: EIU was produced in rats by hind footpad injection of LPS (100 g/animal). Animals were killed 20 h after LPS injection. Inflammation was evaluated by anterior chamber determination of proteins and cells. Results: A dosage of 400 mg/kg per day of thalidomide was efficient in reducing inflammation whether given in three doses (at – 24 h, – 4 h and + 4 h relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two doses (–4 h and +4 h = THAL-2; p < 0.001 for proteins, p < 0.012 for cells) or in one dose (at +4 h=late THAL; p < 0.001 for proteins, p0.02 for cells). A dosage of 300 mg/kg per day of thalidomide was still efficient (p0.023 for proteins, p0.06 for cells), but 150 mg/kg per day had no effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory effect (p 0.053 for proteins, p < 0.06 for cells). Conclusion: High-dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses were not sufficient to reduce inflammation. At similar high doses, supidimide had some effect on EIU but was less effective than thalidomide.These data were presented in part at the first annual ECORA meeting, 4–6 October, 1993, Bonn, Germany     

内毒素诱导的葡萄膜炎动物模型研究进展

葡萄膜炎是一种常见的眼部炎症,易反复发作且牵涉到眼内多种组织,其具体发病机制目前尚不清楚,因此有必要建立合适的动物模型以进行研究。已有研究表明,内毒素注射可以诱导动物的实验性葡萄膜炎。内毒素诱导的葡萄膜炎（EIU）动物模型已成为人们研究葡萄膜炎重要的动物模型,它对人们了解葡萄膜炎的发病机制及治疗葡萄膜炎做出了重要贡献。就该模型的发现、建立方法、炎症过程以及模型中涉及到的内毒素信号通路相关转录因子、细胞因子和一氧化氮（NO）等进行综述。     

Effects of Leukotriene B(4) Receptor Antagonist on Experimental Autoimmune Uveoretinitis in Rats

Purpose: We evaluated the potential of leukotriene B(4) receptor antagonist (LTB(4) RA) as an anti-inflammatory agent on experimental autoimmune uveoretinitis (EAU).Materials and Methods: LTB(4) RA was administered to Lewis rats twice a day on days 0-10, 0-5, and 6-10 after immunization. Rats treated on days 0-10 after immunization were subdivided into three groups according to the dosage of LTB(4) RA. The eyes were examined histopathologically, and the expression of CD 45 RC in CD(+)T cells was analyzed.Results: The inflammatory changes in the eyes of EAU were decreased in all groups treated with LTB(4) RA in a dose-dependent manner. The treatment with LTB(4) RA on days 0-10 after immunization achieved much higher uveitis suppression. The infiltration into eye tissues by neutrophils and lymphocytes was decreased by treatment with LTB(4) RA. In treated groups, the CD 45 RC(high) subset decreased in the induction phase of EAU as compared with the untreated group.Conclusion: The suppressive mechanisms of LT-B(4) RA on EAU may be dependent on suppression of the activation of neutrophils and CD 4(+)T cells.     

Intraocular production of a cytokine (CINC) responsible for neutrophil infiltration in endotoxin induced uveitis.

AIMS/BACKGROUND: The subcutaneous injection of bacterial endotoxin in Lewis rats produces an acute intraocular inflammation evolving over a 24 hour period. This endotoxin induced uveitis (EIU) is characterised by a biphasic protein exudation and a cellular infiltrate composed of macrophages and polymorphonuclear neutrophils (PMNs). This model was used to study the mechanism of cellular infiltration in ocular inflammation. METHODS: EIU was induced by a subcutaneous injection of lipopolysaccharide (LPS) (S typhimurium) at 350 micrograms/kg. The levels of cytokine induced neutrophil chemoattractant (CINC) were measured every 2 hours in the serum and in the aqueous humour by ELISA. The intraocular inflammation was quantified by protein measurement and leucocyte counting. RESULTS: The kinetics of CINC production in the systemic circulation showed a rapid rise, peaking 2 hours after LPS injection, followed by a progressive decline over the next 8 hours. In the eye, the CINC levels increased above the serum levels 10 hours after EIU induction corresponding to the time of cellular infiltration. When leucocyte entry in the eye was inhibited by 56% and 64% with an antiadhesion molecule antibody, there was only a slight reduction in the aqueous humour CINC levels of 9% and 16%, respectively, indicating that CINC was produced by ocular tissue cells. The specific effect of CINC in the eye was confirmed when a direct intraocular injection of 250 ng of purified CINC was followed by significant PMN infiltration, in the absence of protein exudation. CONCLUSION: The data indicate that the production of the CINC chemotactic factor by ocular tissue participates in the inflammatory reaction in EIU.