interleukin-8 and Corneal-Ulcer

Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined.. The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points.. Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the beta galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells.. Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.

Topics: Adenoviridae; Animals; Cornea; Corneal Ulcer; Genetic Vectors; Immunohistochemistry; Interleukin-8; Mice; Mice, SCID; Ophthalmic Solutions; Transduction, Genetic

Ocular infection with Pseudomonas aeruginosa triggers extensive host inflammatory response and corneal damage. The purpose of present study was to investigate the gene expression of pro-inflammatory mediators interleukin (IL)-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha),macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (KC) in the mouse eye challenged with P. aeruginosa. Scratched mouse corneas were infected with three phenotypes of P. aeruginosa individually. Total RNA was extracted from mouse eyes at 4 h, 8 h,16 h and 24 h post-challenge. Single stranded cDNA was synthesized from total RNA by reverse transcription and then subjected to polymerase chain reaction (PCR) using specific primers for IL-1 beta, IL-6, TNF-alpha, MIP-2 and KC. Results revealed three patterns of cytokines and chemokines expression in response to ocular infection with three phenotypes of P. aeruginosa. Ocular infection with the invasive strain induced the highest levels of IL-1 beta, IL-6, MIP-2 and KC mRNA, followed by the infection with the cytotoxic strain. Ocular infection with the CLARE strain induced the lowest levels of IL-1 beta, IL-6, MIP-2 and KC mRNA. The expression of TNF-alpha mRNA was very low and irregular following P. aeruginosa challenge. These data indicate that over-expression of pro-inflammatory cytokines and chemokines may represent a vigorous immune response and therefore may contribute to corneal damage during P. aeruginosa infection.

Topics: Animals; Chemokine CXCL2; Chemokines; Cornea; Corneal Ulcer; Cytokines; Eye Infections, Bacterial; Female; Gene Expression; Interleukin-1; Interleukin-6; Interleukin-8; Mice; Mice, Inbred BALB C; Models, Animal; Monokines; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

To evaluate whether interleukin-8 (IL-8) and RANTES (regulated on activation, normal T-cell expressed and secreted) concentrations in the supernatants of conjunctival epithelial samples from patients with vernal keratoconjunctivitis (VKC) correlate with the number of infiltrating eosinophils or neutrophils and with the severity of corneal lesions.. Thirty-four patients with VKC, 5 patients with seasonal allergic conjunctivitis, and 10 volunteers without allergic diseases were enrolled in this study. Conjunctival epithelial cells were collected by brush cytology and the number of inflammatory cells was counted. The chemokine expression in the cells was investigated by immunocytochemistry and the chemokine concentrations of the cell suspensions were measured by enzyme-linked immunosorbent assay.. The percentages of eosinophils and neutrophils in cell suspensions from VKC patients with corneal erosion or ulcer were higher than those from subjects with clear corneas or superficial punctate keratopathy. IL-8 concentrations in the supernatant of samples correlated significantly with the percentages of neutrophils and eosinophils in paired cell suspensions. No correlation was observed between RANTES and the percentages of eosinophils. Positive staining for IL-8 was observed in the cytosol of conjunctival epithelial cells.. IL-8 in the extracellular space of the conjunctival epithelium may play a role in the recruitment of neutrophils and possibly eosinophils and in the pathogenesis of corneal damage in severe allergic diseases.

Topics: Adolescent; Adult; Aged; Chemokine CCL5; Child; Conjunctiva; Conjunctivitis, Allergic; Corneal Ulcer; Cytological Techniques; Enzyme-Linked Immunosorbent Assay; Eosinophils; Epithelium; Female; Humans; Immunoenzyme Techniques; Interleukin-8; Male; Neutrophil Infiltration

Contact lens induced acute red eye (CLARE) and contact lens induced peripheral ulcer (CLPU) are among the most common contact lens induced inflammatory reactions. Both CLARE and CLPU are characterized by corneal infiltration which indicates the presence of chemoattractants and other inflammatory mediators. The aim of this study was to characterize the cytokine and chemotactic lipid inflammatory mediator profile in the tears of people experiencing CLARE or CLPU. Cytokines IL-1 beta, IL-6, IL-8, GM-CSF and LTB4 in tears were measured by antibody sandwich and competition inhibition enzyme-linked immunosorbent assays (ELISA). Platelet activating factor-like activity was measured by a degranulation assay by measuring the release of labelled serotonin from platelets. The functional role GM-CSF and chemoattractants were determined by flow cytometry and chemotaxis. Increased levels of cytokines and chemoattractants were detected in both CLARE and CLPU tears. CLPU tears showed increased levels of LTB4 (P = 0.002) and PAF-like activity (P = 0.047) whereas CLARE tears showed increased levels of GM-CSF (P = 0.002). IL-8 (P < 0.05). LTB4 (P = 0.002) and PAF-like activity (P = 0.047) compared to control tears. Flow cytometric analysis revealed that incubation of PMN with CLARE tears increased the number of IgA receptors indicating that the GM-CSF in CLARE tears was active. Combinations of suboptimal concentrations (which were found in CLARE and CLPU tears) of IL-8 with either LTB4 or PAF significantly (P < 0.0001) enhanced the chemotactic activity for PMN compared to their individual effects. Our data highlight the possible pathophysiological roles of these inflammatory mediators in leukocyte recruitment and activation during ocular inflammatory responses. The results suggests that GM-CSF, IL-8 and LTB4 are active during corneal pathology and LTB4 or IL-8 may maintain the contact lens induced PMN response in vivo.

Topics: Acute Disease; Analysis of Variance; Cells, Cultured; Contact Lenses; Corneal Ulcer; Cytokines; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation Mediators; Interleukin-8; Keratitis; Leukotriene B4; Lipids; Neutrophil Activation; Neutrophils; Platelet Activating Factor; Receptors, Fc; Tears