Staphylococcus is a leading cause of the potentially blinding disease microbial keratitis. Even with the use of antibiotic therapy, the host inflammatory response continues to damage the cornea, which may lead to blindness. Manipulation of the host response may help improve patient outcome from this devastating disease. We aim to understand the contribution of the host response to Staphylococcus aureus infection. A S. aureus keratitis mouse model was developed in both C57BL/6 and BALB/c mice using two different strains of S. aureus (8325‐4 and Staph 38). Twenty‐four hours postinfection, mice were killed and eyes were harvested for enumeration of bacteria, polymorphonuclear leucocytes, chemokines and cytokines. The laboratory strain 8325‐4 was not as virulent as the clinical isolate Staph 38. In vitro data showed a 250‐fold increase in invasion of human corneal epithelial cells by Staph 38 compared to 8325‐4. BALB/c mice were susceptible to S. aureus infection whereas C57BL/6 mice were resistant. The resistant C57BL/6 mice were polarized towards a Th2 response, which may be protective for these mice. IL‐4, IL‐10 and IL‐6 were elevated significantly in C57BL/6 mice infected with Staph 38 (P < 0.05). Macrophage inflammatory peptide (MIP)‐2 was also significantly elevated in C57BL/6 mice (P < 0.001). The susceptible BALB/c mice had a muted cytokine response, which suggests that S. aureus might be ‘walled off’ during infection and might avoid host defences. IL‐4, IL‐10 and IL‐6 cytokines may be protective during Gram‐positive corneal infection and therefore may be useful for adjunct therapies in the treatment of this disease.
Objectives: The objectives of this study were to determine whether a synergistic effect could be obtained in vitro between bovine lactoferricin (B-LFcin) and antibiotics against Pseudomonas aeruginosa and Staphylococcus aureus isolates from ocular infections, and to evaluate the use of B-LFcin as an adjunct to the antibiotic treatment of corneal infection in vivo.Methods: Chequerboard and time -kill assays were performed to investigate the combined effects of B-LFcin and conventional antibiotics, including ciprofloxacin, ceftazidime and gentamicin, against 17 strains of P. aeruginosa (8) and S. aureus (9) isolated from ocular infection and inflammation, and 1 reference strain of S. aureus. Corneas of C57BL/6 mice were topically challenged with a multidrug-resistant strain of P. aeruginosa. Nine hours post-challenge, mice were treated topically and hourly with either vehicle, B-LFcin, ciprofloxacin or ciprofloxacin containing B-LFcin for 8 h. Corneas were then clinically examined, and bacterial numbers and levels of myeloperoxidase (MPO) evaluated.Results: Synergy between B-LFcin and ciprofloxacin or ceftazidime was identified in most P. aeruginosa isolates, including multidrug-resistant strains, whereas no synergistic effect was seen between B-LFcin and gentamicin. Synergy was only observed with B-LFcin and ciprofloxacin against 2/10 S. aureus strains, and there was no synergy between B-LFcin and any of the other antibiotics tested. Combined B-LFcin and ciprofloxacin treatment significantly improved the clinical outcome, and reduced bacterial numbers and MPO in infected mouse corneas. B-LFcin alone was also able to reduce levels of MPO in infected corneas.Conclusions: These findings indicate that B-LFcin may have advantages as an adjunct therapy with both antimicrobial and anti-inflammatory properties in the treatment of corneal infection. Keywords: keratitis, Pseudomonas aeruginosa, Staphylococcus aureus, ciprofloxacin IntroductionSince their introduction, antibiotics have been the mainstay of treatment for bacterial infections.1 However, increasing bacterial resistance to antimicrobials is rapidly becoming a major public health concern.2,3 In response to increasing bacterial resistance, the fluoridated 4-quinolones, such as ciprofloxacin, were introduced in the 1980s. Now, there are increasing reports of resistance to this class of drugs in clinical isolates, particularly Pseudomonas aeruginosa and Staphylococcus aureus, with high levels of resistance being reported in cases of microbial keratitis. 4 Microbial keratitis is a relatively rare but severe disease of the cornea, which can lead to blindness and vision loss as a result of scarring or perforation of the cornea if appropriate antibiotic therapy is not rapidly instituted. S. aureus is the most common pathogen associated with microbial keratitis of all causes, 5 while P. aeruginosa is regarded as a major causative pathogen for contact lens-associated microbial keratitis and represents 40% -70% of clinical isolates from microbial keratitis associated with...
Ambient PM10 is likely to be more important than traffic-derived PM in causing injury to AEC leading to production of pro-inflammatory cytokines. The injurious effects may be related to the presence of iron in the coarse fraction of airborne PM. These findings are likely to be relevant to the pathogenesis of asthma.
The data suggest an important regulatory role for IL-6 in modulating excessive inflammatory responses and in controlling bacterial proliferation. IL-6 may play a role in the priming and activation of neutrophils. It could represent a broad-spectrum therapy to improve outcomes in patients who have these potentially blinding infections.
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