This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thakur, A.
Right arrow Articles by Willcox, M. D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thakur, A.
Right arrow Articles by Willcox, M. D. P.

 Previous Article  |  Next Article 

Infection and Immunity, April 2002, p. 2187-2197, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2187-2197.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Balance of Pro- and Anti-Inflammatory Cytokines Correlates with Outcome of Acute Experimental Pseudomonas aeruginosa Keratitis

A. Thakur,1* M. Xue,1 F. Stapleton,1 A. R. Lloyd,2 D. Wakefield,2 and M. D. P. Willcox1

Cornea and Contact Lens Research Unit, Cooperative Research Centre for Eye Research and Technology,1 Inflammation Research Unit, School of Pathology, The University of New South Wales, Sydney, New South Wales 2052, Australia2

Received 20 July 2001/ Returned for modification 20 September 2001/ Accepted 16 November 2001

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 x 106 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, enzyme-linked 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-1ß (IL-1ß), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1ß 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-1ß. 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.

* Corresponding author. Present address: Department of Anatomy and Cell Biology, School of Medicine, Wayne State University, 540 E. Canfield Ave., Detroit, MI 48201. Phone: (313) 577-1074. Fax: (313) 577-3125. E-mail: a.thakur{at}med.wayne.edu.

Editor: J. D. Clements

Infection and Immunity, April 2002, p. 2187-2197, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2187-2197.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kondo, Y., Fukuda, K., Adachi, T., Nishida, T. (2008). Inhibition by a Selective I{kappa}B Kinase-2 Inhibitor of Interleukin-1-Induced Collagen Degradation by Corneal Fibroblasts in Three-Dimensional Culture. IOVS 49: 4850-4857 [Abstract] [Full Text]  
  • Huang, L. C., Reins, R. Y., Gallo, R. L., McDermott, A. M. (2007). Cathelicidin-Deficient (Cnlp / ) Mice Show Increased Susceptibility to Pseudomonas aeruginosa Keratitis. IOVS 48: 4498-4508 [Abstract] [Full Text]  
  • Hume, E. B. H., Cole, N., Garthwaite, L. L., Khan, S., Willcox, M. D. P. (2006). A Protective Role for IL-6 in Staphylococcal Microbial Keratitis. IOVS 47: 4926-4930 [Abstract] [Full Text]  
  • Lu, Y., Fukuda, K., Nakamura, Y., Kimura, K., Kumagai, N., Nishida, T. (2005). Inhibitory Effect of Triptolide on Chemokine Expression Induced by Proinflammatory Cytokines in Human Corneal Fibroblasts. IOVS 46: 2346-2352 [Abstract] [Full Text]  
  • Lu, Y., Fukuda, K., Liu, Y., Kumagai, N., Nishida, T. (2004). Dexamethasone Inhibition of IL-1-Induced Collagen Degradation by Corneal Fibroblasts in Three-Dimensional Culture. IOVS 45: 2998-3004 [Abstract] [Full Text]  
  • Thakur, A., Barrett, R. P., Hobden, J. A., Hazlett, L. D. (2004). Caspase-1 Inhibitor Reduces Severity of Pseudomonas aeruginosa Keratitis in Mice. IOVS 45: 3177-3184 [Abstract] [Full Text]  
  • Lu, Y., Fukuda, K., Seki, K., Nakamura, Y., Kumagai, N., Nishida, T. (2003). Inhibition by Triptolide of IL-1-Induced Collagen Degradation by Corneal Fibroblasts. IOVS 44: 5082-5088 [Abstract] [Full Text]  
  • Li, Q., Fukuda, K., Lu, Y., Nakamura, Y., Chikama, T.-i., Kumagai, N., Nishida, T. (2003). Enhancement by neutrophils of collagen degradation by corneal fibroblasts. J. Leukoc. Biol. 74: 412-419 [Abstract] [Full Text]  
  • McClellan, S. A., Huang, X., Barrett, R. P., van Rooijen, N., Hazlett, L. D. (2003). Macrophages Restrict Pseudomonas aeruginosa Growth, Regulate Polymorphonuclear Neutrophil Influx, and Balance Pro- and Anti-Inflammatory Cytokines in BALB/c Mice. J. Immunol. 170: 5219-5227 [Abstract] [Full Text]  
  • Xue, M. L., Wakefield, D., Willcox, M. D. P., Lloyd, A. R., Di Girolamo, N., Cole, N., Thakur, A. (2003). Regulation of MMPs and TIMPs by IL-1{beta} during Corneal Ulceration and Infection. IOVS 44: 2020-2025 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»