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. 1999;8(3):159–167. doi: 10.1080/09629359990496

Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.

A L Pukhalsky 1, N I Kapranov 1, E A Kalashnikova 1, G V Shmarina 1, L A Shabalova 1, S N Kokarovtseva 1, D A Pukhalskaya 1, N J Kashirskaja 1, O I Simonova 1
PMCID: PMC1781793  PMID: 10704054

Abstract

Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy.

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Selected References

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  1. Anwar H., Strap J. L., Costerton J. W. Susceptibility of biofilm cells of Pseudomonas aeruginosa to bactericidal actions of whole blood and serum. FEMS Microbiol Lett. 1992 May 1;71(3):235–241. doi: 10.1016/0378-1097(92)90715-z. [DOI] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Brogdon W. G., Dickinson C. M. A microassay system for measuring esterase activity and protein concentration in small samples and in high-pressure liquid chromatography eluate fractions. Anal Biochem. 1983 Jun;131(2):499–503. doi: 10.1016/0003-2697(83)90204-x. [DOI] [PubMed] [Google Scholar]
  4. Fick R. B., Jr, Sonoda F., Hornick D. B. Emergence and persistence of Pseudomonas aeruginosa in the cystic fibrosis airway. Semin Respir Infect. 1992 Sep;7(3):168–178. [PubMed] [Google Scholar]
  5. Fuqua C., Winans S. C., Greenberg E. P. Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu Rev Microbiol. 1996;50:727–751. doi: 10.1146/annurev.micro.50.1.727. [DOI] [PubMed] [Google Scholar]
  6. Giwercman B., Jensen E. T., Høiby N., Kharazmi A., Costerton J. W. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrob Agents Chemother. 1991 May;35(5):1008–1010. doi: 10.1128/aac.35.5.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Govan J. R., Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev. 1996 Sep;60(3):539–574. doi: 10.1128/mr.60.3.539-574.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Govan J. R., Harris G. S. Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis. Microbiol Sci. 1986 Oct;3(10):302–308. [PubMed] [Google Scholar]
  9. Graham A., Hasani A., Alton E. W., Martin G. P., Marriott C., Hodson M. E., Clarke S. W., Geddes D. M. No added benefit from nebulized amiloride in patients with cystic fibrosis. Eur Respir J. 1993 Oct;6(9):1243–1248. [PubMed] [Google Scholar]
  10. Gray K. M. Intercellular communication and group behavior in bacteria. Trends Microbiol. 1997 May;5(5):184–188. doi: 10.1016/S0966-842X(97)01002-0. [DOI] [PubMed] [Google Scholar]
  11. Heeckeren A., Walenga R., Konstan M. W., Bonfield T., Davis P. B., Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J Clin Invest. 1997 Dec 1;100(11):2810–2815. doi: 10.1172/JCI119828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heeckeren A., Walenga R., Konstan M. W., Bonfield T., Davis P. B., Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J Clin Invest. 1997 Dec 1;100(11):2810–2815. doi: 10.1172/JCI119828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Høiby N., Koch C. Cystic fibrosis. 1. Pseudomonas aeruginosa infection in cystic fibrosis and its management. Thorax. 1990 Nov;45(11):881–884. doi: 10.1136/thx.45.11.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Joris L., Dab I., Quinton P. M. Elemental composition of human airway surface fluid in healthy and diseased airways. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1633–1637. doi: 10.1164/ajrccm/148.6_Pt_1.1633. [DOI] [PubMed] [Google Scholar]
  15. Kleerebezem M., Quadri L. E., Kuipers O. P., de Vos W. M. Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria. Mol Microbiol. 1997 Jun;24(5):895–904. doi: 10.1046/j.1365-2958.1997.4251782.x. [DOI] [PubMed] [Google Scholar]
  16. Koch C., Høiby N. Pathogenesis of cystic fibrosis. Lancet. 1993 Apr 24;341(8852):1065–1069. doi: 10.1016/0140-6736(93)92422-p. [DOI] [PubMed] [Google Scholar]
  17. Konstan M. W., Hilliard K. A., Norvell T. M., Berger M. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Respir Crit Care Med. 1994 Aug;150(2):448–454. doi: 10.1164/ajrccm.150.2.8049828. [DOI] [PubMed] [Google Scholar]
  18. Learn D. B., Brestel E. P., Seetharama S. Hypochlorite scavenging by Pseudomonas aeruginosa alginate. Infect Immun. 1987 Aug;55(8):1813–1818. doi: 10.1128/iai.55.8.1813-1818.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Massion P. P., Inoue H., Richman-Eisenstat J., Grunberger D., Jorens P. G., Housset B., Pittet J. F., Wiener-Kronish J. P., Nadel J. A. Novel Pseudomonas product stimulates interleukin-8 production in airway epithelial cells in vitro. J Clin Invest. 1994 Jan;93(1):26–32. doi: 10.1172/JCI116954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pedersen S. S. Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis. APMIS Suppl. 1992;28:1–79. [PubMed] [Google Scholar]
  21. Pier G. B. Pulmonary disease associated with Pseudomonas aeruginosa in cystic fibrosis: current status of the host-bacterium interaction. J Infect Dis. 1985 Apr;151(4):575–580. doi: 10.1093/infdis/151.4.575. [DOI] [PubMed] [Google Scholar]
  22. Pukhalsky A. L., Kalashnikova E. A., Lyashko V. N., Pevnitsky L. A. Inhibition of phytohemagglutinin-induced lymphocyte proliferation by dexamethasone: mechanisms of individual susceptibility. Int J Immunopharmacol. 1990;12(6):657–663. doi: 10.1016/0192-0561(90)90103-t. [DOI] [PubMed] [Google Scholar]
  23. Ruef C., Jefferson D. M., Schlegel-Haueter S. E., Suter S. Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. Eur Respir J. 1993 Nov;6(10):1429–1436. [PubMed] [Google Scholar]
  24. Simpson J. A., Smith S. E., Dean R. T. Scavenging by alginate of free radicals released by macrophages. Free Radic Biol Med. 1989;6(4):347–353. doi: 10.1016/0891-5849(89)90078-6. [DOI] [PubMed] [Google Scholar]
  25. Smith J. J., Travis S. M., Greenberg E. P., Welsh M. J. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell. 1996 Apr 19;85(2):229–236. doi: 10.1016/s0092-8674(00)81099-5. [DOI] [PubMed] [Google Scholar]
  26. Suter S., Schaad U. B., Roux L., Nydegger U. E., Waldvogel F. A. Granulocyte neutral proteases and Pseudomonas elastase as possible causes of airway damage in patients with cystic fibrosis. J Infect Dis. 1984 Apr;149(4):523–531. doi: 10.1093/infdis/149.4.523. [DOI] [PubMed] [Google Scholar]
  27. Van Delden C., Iglewski B. H. Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis. 1998 Oct-Dec;4(4):551–560. doi: 10.3201/eid0404.980405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Visser L., Blout E. R. The use of p-nitrophenyl N-tert-butyloxycarbonyl-L-alaninate as substrate for elastase. Biochim Biophys Acta. 1972 Apr 7;268(1):257–260. doi: 10.1016/0005-2744(72)90223-9. [DOI] [PubMed] [Google Scholar]
  29. Wheeler W. B., Colten H. R. Cystic fibrosis: current approach to diagnosis and management. Pediatr Rev. 1988 Feb;9(8):241–248. doi: 10.1542/pir.9-8-241. [DOI] [PubMed] [Google Scholar]

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