interleukin-8 and Uveitis--Anterior

The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.

Topics: Adult; Aqueous Humor; Cell Movement; Cells, Cultured; Chemokine CCL2; Cytomegalovirus; Extracellular Matrix Proteins; Eye Infections, Viral; Herpesvirus 1, Human; Humans; Interleukin-8; Middle Aged; Primary Cell Culture; Receptors, CCR2; Receptors, Interleukin-8A; Trabecular Meshwork; Uveitis, Anterior

To describe and to compare the clinical manifestation and laboratory test results of herpetic anterior uveitis (HAU) caused by Herpes simplex virus (HSV) and varicella-zoster virus (VZV).. A retrospective, observational study on patients diagnosed with HAU. Etiology, clinical features, ocular complications, and recurrences of the infection were evaluated as main clinical parameters. The aqueous Interleukin-8 (IL-8) level was also measured to assess the intraocular inflammation.. Thirty-two eyes (32 patients) were involved. Among all involved cases, 24 had VZV-AU and 8 had HSV-AU. Common clinical features of HAU included the presence of KPs (90.6%), distorted pupil (83.3%), Iris atrophy (71.9%) and corneal edema (50%). The intraocular fluid analysis showed higher viral load and IL-8 level in VZV-AU.. Compared with HSV-AU, the intraocular inflammation was more severe in VZV-AU. The intraocular fluid analysis was valuable for the etiological diagnosis and the evaluation of disease severity.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Aqueous Humor; Asian People; China; Drug Therapy, Combination; Eye Infections, Viral; Female; Glucocorticoids; Herpes Zoster Ophthalmicus; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Interleukin-8; Male; Middle Aged; Referral and Consultation; Retrospective Studies; Simplexvirus; Uveitis, Anterior; Valacyclovir; Viral Load; Visual Acuity; Young Adult

Uveitis is the inflammation of the uvea that often occurs in children. There are many causes of disease, but some of them do not have any reasons and are then called idiopathic uveitis. Cytokines play an important role in the regulation of the immune response. Determination of cytokine profiles could contribute to the explanation of the etiology of uveitis and could serve to evaluate the inflammation intensity as well as be helpful in the early diagnosis this disease. The purpose of this study was to determine the serum level of selected inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α) and to compare their diagnostic power as a markers of idiopathic anterior uveitis in children.. The study was carried out on 28 children diagnosed with idiopathic anterior uveitis. The reference group comprised 30 healthy children. Serum IL-6, IL-8, and TNF-α concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods.. The mean values of IL-6, IL-8, and TNF-α in the children with idiopathic anterior uveitis were significantly higher than those found in the reference group. The highest sensitivity, specificity, accuracy, positive and negative predictive value, and likelihood ratio of a positive test result were achieved for IL-8. There was a significant difference between the area under the curve for IL-6 and IL-8.. Increased serum concentrations of interleukin IL-6, IL-8, and TNF-α may suggest that these cytokines induce inflammatory changes in the ocular surface. Analysis of cytokine levels showed that IL-8 has the highest diagnostic power and is the best marker for diagnosis of idiopathic anterior uveitis in children.

Topics: Adolescent; Child; Humans; Interleukin-6; Interleukin-8; ROC Curve; Tumor Necrosis Factor-alpha; Uveitis, Anterior

To evaluate whether NETosis is involved in cytokine-induced ocular inflammation and to track neutrophil extracellular traps (NET) complexes in patients with proliferative diabetic retinopathy (PDR).. For the animal model, the eyes of C57BL/6J mice were intravitreally injected with interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), or saline. Histology and immunofluorescence staining for CD11b, neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone 3 (H3Cit), and net-like structure were performed. Vitreous samples were collected from patients with PDR; the PDR1 group had no need for repeated surgical intervention, and the PDR2 group had repeated vitreous bleeding or other complication and controls. Levels of MPO, H3Cit-MPO, and NE-MPO complex were measured with enzyme-linked immunosorbent assay (ELISA).. Massive influx of CD11+ inflammatory cells, involving the anterior and posterior chambers, was observed in the murine eyes 24 h after the IL-8 or TNF-α injections. Cells excreted to their surroundings an extracellular net-like structure positive for NE, MPO, and H3Cit. H3Cit staining was abolished with the DNase I treatment, indicating the presence of extracellular DNA in the net-like structures. The vitreous samples of the patients with PDR2 contained statistically significantly higher levels of MPO (173±230) compared to those of the patients with PDR1 (12.0±33.0, p<0.05) or the controls (0.00, p<0.01). The levels of H3Cit-MPO and NE-MPO complexes were also statistically significantly higher in the patients with PDR2 (776.0±1274, 573.0±911.0, respectively) compared to those in the patients with PDR1 (0, p<0.05) and the controls (0, p<0.05).. This study showed the existence of NETosis in cytokine-induced ocular inflammation in a mouse model and human samples. Furthermore, the extent of NET complex formation was higher in a subset of patients who exhibited more complicated PDR.

Topics: Adult; Aged; Animals; Diabetic Retinopathy; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Extracellular Traps; Female; Histones; Humans; Inflammation; Interleukin-8; Leukocyte Elastase; Male; Mice; Mice, Inbred C57BL; Middle Aged; Peroxidase; Tumor Necrosis Factor-alpha; Uveitis, Anterior; Uveitis, Posterior; Vitreous Body

To examine the potential therapeutic effect of a neutralizing anti-IL-8 monoclonal antibody in endotoxin-induced uveitis (EIU) in the rabbit.. An anti-IL-8 antibody (WS-4) was injected intravitreal 2 hours before, simultaneously with, or 6 hours after endotoxin challenge in rabbits. Eyes were examined for clinical signs of inflammation, and aqueous humor (AH) was sampled to study cellular infiltration and protein content. Leukocyte subset analysis was performed on Giemsa-stained AH cytospins. Histologic grading of inflammation was performed on hematoxylin-eosin-stained sagittal sections of enucleated eyes. In separate experiments, animals received the anti-IL-8 antibody simultaneously with the endotoxin challenge, before repeated anterior chamber paracentesis was performed (at 6, 12, 24, 48, and 72 hours after injection) to estimate the kinetics and durability of changes in total cell count and protein concentration in AH.. Anti-IL-8 therapy caused a decrease in the clinical and histologic grade of inflammation in EIU. The mean cell count in the AH at the peak of inflammation (24 hours) in eyes receiving endotoxin only was 6419+/-1165/microl (mean +/- SE) compared to 2546+/-573/microl in rabbits treated simultaneously with 250 microg of anti-IL-8 antibody (P < 0.05). The protein concentration in the AH was not significantly altered by anti-IL-8 treatment. Kinetic analysis of the leukocyte count in the AH demonstrated persistent inhibition of leukocyte accumulation (range, 60%-91% compared to control eyes) by the anti-IL-8 antibody administered simultaneously with endotoxin. This inhibition was sustained for up to 72 hours after injection.. Anti-IL-8 antibody treatment partially blocks EIU in rabbits. A consistent decrease in the recruitment of polymorphonuclear leukocytes into the anterior chamber was obtained when neutralizing antibody was injected simultaneously with endotoxin. These findings suggest that IL-8 contributes to the chemotactic signal for the recruitment of leukocytes in EIU.

Topics: Animals; Anterior Eye Segment; Antibodies, Monoclonal; Aqueous Humor; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Eye Proteins; Female; Interleukin-8; Leukocyte Count; Lipopolysaccharides; Neutrophils; Rabbits; Recombinant Proteins; Salmonella typhimurium; Uveitis, Anterior

To find a laboratory indicator for systemic involvement in intermediate uveitis.. Interleukin 8 (IL-8) and C reactive protein (CRP) serum levels were measured in patients with idiopathic intermediate uveitis (n = 61), uveitis controls (n = 143), and normal controls (n = 29). The records of those with intermediate uveitis were reviewed with the emphasis on disease activity and severity as characterised by the presence of cystoid macular oedema, vitreous exudates or snowbank formation, papillitis, and periphlebitis.. Increased serum IL-8 (> or = 20 pg/ml) was found in 27 out of 61 patients with intermediate uveitis (p < 0.01), 12 of 27 patients with sarcoid uveitis (p < 0.05), in 19 of 30 patients with HLA-B27 associated acute anterior uveitis (p < 0.05), and in five of 29 healthy controls. Raised IL-8 levels in intermediate uveitis were significantly associated with active disease (p < 0.001) and the presence of vitreous exudates (p < 0.001), papillitis, and periphlebitis (p < 0.01). Elevated CRP levels were found in 12 of the 143 uveitis controls but in none of the intermediate uveitis patients or normal controls. During follow up an associated systemic disease was more frequently noticed in patients with an elevated serum IL-8 at entry into the study.. Elevated IL-8 serum levels were found in patients with active intermediate uveitis of unknown origin. An elevated IL-8 level seems to predispose the patient to a later development of associated systemic disease.

Topics: Adult; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; HLA-B27 Antigen; Humans; Interleukin-8; Male; Middle Aged; Sarcoidosis; Severity of Illness Index; Uveitis, Anterior; Uveitis, Intermediate

Studies from our laboratory have demonstrated the release of high levels of neutrophil chemotactic factors (NCF) from isolated rabbit corneas injured by hydrogen peroxide (H2O2). The purpose of the present study was to determine the biological activity of these factors and to test the hypothesis that the intracameral injection of these factors can induce inflammation of the anterior segment. Under sterile conditions, the epithelial surfaces of isolated rabbit corneas were incubated with a 300 ul mixture of glucose (G) (1mg/ml) and glucose oxidase (GO) (20 U/ml) at 37 degrees C for 6 hours. This supernatant solution was collected and a 100 ul sample containing NCF, but not H2O2, was injected into the anterior chamber of anesthetized rabbit eyes (n = 8). Anterior chamber inflammation, characterized by moderate corneal edema associated with a fibrinous anterior chamber reaction, was evident 2 and 4 hours after injection. Aqueous humor analysis revealed the presence of fibrin and a large number of neutrophils (32 +/- 5 x 10(4) cells/ml). Control eyes, on the other hand, showed normal morphology and low levels of neutrophils after the injection of 100 ul minimum essential medium (MEM) (n = 8) (1.2 +/- 0.14 x 10(4) cells/ml), G/GO mixture (n = 8) (5 +/- 0.86 x 10(4) cells/ml), or supernatant solutions collected from MEM-treated corneas (n = 8) (15 +/- 2 x 10(4) cells/ml). To determine whether the inflammatory reaction observed was due to a direct effect of the chemoattractants or mediated through stimulation of arachidonic acid (AA) metabolites, we pretreated rabbit eyes with a sterile solution of 0.1% dexamethasone (n = 8 eyes) or with a sterile solution of 3.4% indomethacin (n = 8 eyes) three times a day, for one day, prior to the injection of NCF supernatant solution. Examination 2 hours and 4 hours after injection revealed inflammation characterized by mild-to-moderate corneal edema associated with a fibrinous anterior chamber reaction was observed with or without prior treatment with AA metabolite inhibitors. No difference in the degree of inflammation was detected clinically. Results of these studies suggest that NCF released from H2O2-injured corneas can directly induce inflammation of the anterior segment, and that metabolites of AA are not mediating the observed in vivo response.

Topics: Animals; Anterior Chamber; Aqueous Humor; Cornea; Dexamethasone; Female; Hydrogen Peroxide; Indomethacin; Injections; Interleukin-8; Male; Neutrophils; Rabbits; Uveitis, Anterior