An Ocular Strain ofPseudomonas aeruginosais Inflammatory but not Virulent in the Scarified Mouse Model

Cowell, Brigitte A.; Willcox, Mark; Hobden, Jeffery A.; Schneider, René Peter; Tout, S.; Hazlett, Linda D.

doi:10.1006/exer.1998.0524

Cited by 31 publications

(27 citation statements)

References 22 publications

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“…PMN in whole eyes were quantitated by determining myeloperoxidase activity (11). Viable bacteria in whole eyes (n ϭ 5) were quantitated as described by Cowell et al (5). Data were examined statistically using an unpaired Student t test.…”

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confidence: 99%

Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection

et al. 2001

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Lack of interleukin-6 (IL-6) during Pseudomonas aeruginosa corneal infection leads to more severe disease with changes in neutrophil recruitment. Exogenous IL-6 leads to increased efficiency of neutrophil recruitment and reduced bacterial loads in corneal infection in both IL-6 gene knockout and wild-type mice. This may be mediated by IL-6 increasing the production of corneal macrophage inflammatory protein 2 and intercellular cell adhesion molecule 1. We conclude that effective recruitment of neutrophils into the cornea is dependent on the production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.Pseudomonas aeruginosa is a leading cause of corneal infection, often resulting in blindness (13). The host inflammatory responses, which are orchestrated by cytokines and chemokines, are critical in determining the outcome of ocular infection with P. aeruginosa (8, 10). Our studies have shown that interleukin-6 (IL-6) is important in protecting the cornea during P. aeruginosa infection (15). Its role appears to be central to the regulation of leukocyte recruitment into the avascular cornea (15). This is consistent with findings in other infection models in IL-6 gene knockout (gko) mice (6,7,12). Other studies using systemic administration of IL-6 in septic shock (3) and listeriosis (14) also support the protective role of IL-6. We have examined the effects of local administration of IL-6 on the outcome of P. aeruginosa infection of the cornea in IL-6 gko and wild-type mice. Our results indicate that effective recruitment of polymorphonuclear neutrophils (PMN) into the cornea is dependent on production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.IL-6 gko in a C57BL/6 ϫ Sv 129 background and the corresponding wild-type mice were obtained from the Jackson Laboratory (Bar Harbour, Maine). Inbred 8-week-old mice were challenged with P. aeruginosa strain 6206 as previously described (4). Solutions of murine IL-6 for injection (2) were prepared in pyrogen-free saline and were administered as 20-l subconjunctival injections containing 100 ng of IL-6. IL-6 was administered 4 h prior to challenge, at the time of challenge, and 6 h postchallenge. Control animals were injected subconjunctivally with 20 l of pyrogen-free, phosphate buffered saline (PBS) on the same schedule. Mice were sacrificed 12 h postchallenge, and their eyes were collected and either formalin fixed or stored at Ϫ70°C for the enzyme-linked immunosorbent assay and the PMN and bacterial number assays. These experiments were performed on at least 12 mice per group and repeated at least twice.

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confidence: 99%

Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection

et al. 2001

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“…(25,26). Both the cytotoxic and invasive strains have been shown to produce large number of proteinases (10,22). By contrast, the CLARE phenotype is neither invasive nor cytotoxic and has been shown to produce low levels of proteinases (10,18).…”

Section: Vol 70 2002 Balance Of Cytokines In Keratitis 2193mentioning

confidence: 99%

“…Both the cytotoxic and invasive strains have been shown to produce large number of proteinases (10,22). By contrast, the CLARE phenotype is neither invasive nor cytotoxic and has been shown to produce low levels of proteinases (10,18). Previous studies with Pseudomonas strains have demonstrated that cytokine production in vivo is correlated to a large extent with the virulence of the pathogen (17,27).…”

Section: Vol 70 2002 Balance Of Cytokines In Keratitis 2193mentioning

confidence: 99%

“…The cytotoxic strains cause a rapid cytotoxicity in the mammalian cells, whereas the invasive strains can remain inside cells for up to 24 h before the cells show any overt cytopathic effect (21). While both cytotoxic and invasive strains can produce large amounts of proteases (10,22), the CLARE strain can produce only low levels (10,18). The invasive and cytotoxic strains were isolated from human microbial keratitis.…”

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confidence: 99%

“…The invasive and cytotoxic strains were isolated from human microbial keratitis. The CLARE strain (Paer1) is not associated with tissue destruction in the cornea but causes the self-limiting condition known as CLARE (10).…”

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confidence: 99%

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Balance of Pro- and Anti-Inflammatory Cytokines Correlates with Outcome of Acute ExperimentalPseudomonas aeruginosaKeratitis

et al. 2002

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The purpose of this study was to elucidate the expression of pro-and anti-inflammatory cytokines in mouse corneas infected with Pseudomonas aeruginosa. Three bacterial strains (invasive, cytotoxic, or CLARE [contact lens-induced acute red eye]) which have recently been shown to produce distinct patterns of corneal disease in the mouse were used. The left mouse (BALB/c) corneas were scarified and infected with 2 ؋ 10 6 CFU of one of the three P. aeruginosa strains, while right eyes served as controls. Animals were examined at 1, 4, 8, 16, and 24 h with a slit lamp biomicroscope to grade the severity of infection. Following examination, eyes were collected and processed for histopathology, multiprobe RNase protection assay for cytokine mRNA, enzymelinked immunosorbent assay to quantitate cytokine proteins, and myeloperoxidase activity to quantitate polymorphonuclear leukocytes. The kinetics of appearance and magnitude of expression of key cytokines varied significantly in the three different phenotypes of P. aeruginosa infection. The predominant cytokines expressed in response to all three phenotypes were interleukin-1␤ (IL-1␤), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1␤ were present at all time points, whereas corneas challenged with the CLARE strain, which induced very mild inflammation, showed a high ratio of IL-1Ra to IL-1␤. The outcome of infection in bacterial keratitis correlated with the relative induction of these pro-and anti-inflammatory cytokines, and exogenous administration of recombinant rIL-1Ra (rIL-1Ra) was able to reduce the disease severity significantly. These findings point to the therapeutic potential of rIL-1Ra protein in possible treatment strategies for bacterial keratitis.

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β-Catenin promotes host resistance against Pseudomonas aeruginosa keratitis

Chen

Yin

Nie

et al. 2013

Journal of Infection

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An Ocular Strain ofPseudomonas aeruginosais Inflammatory but not Virulent in the Scarified Mouse Model

Cited by 31 publications

References 22 publications

Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection

Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection

Balance of Pro- and Anti-Inflammatory Cytokines Correlates with Outcome of Acute ExperimentalPseudomonas aeruginosaKeratitis

β-Catenin promotes host resistance against Pseudomonas aeruginosa keratitis

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