Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Respiratory manifestations may be secondary to inflammation in cystic fibrosis patients


New Evidence That Inflammation For Cystic Fibrosis May Be Present Before Patients Show Respiratory Manifestations.

A new study also provides additional evidence that the persistent and excessive inflammation in the lungs of CF patients involves a failure of the mechanisms that control the inflammatory response.

Cystic Fibrosis (CF) is one of the most frequent lethal chromosomal hereditary disorders in Caucasian populations and occurs in approximately one in every 3,500 births. Caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, a defective cAMP-dependent chloride ion conductance occurs. In patients with CF, lung disease is the major cause of sickness and death with the progressive decline of pulmonary function attributed to a vicious cycle of airway infection and inflammation. There is now evidence that inflammation plays a pivotal role and may be present very early in life, even before the onset of respiratory manifestations.


The inflammatory process in the CF lung is dominated by a polymorphonuclear neutrophil (white blood cell) influx. Accumulation of neutrophils in the airways is associated with high concentrations of neutrophil-derived mediators, in particular pro-inflammatory cytokines (proteins) such as IL-8 and TNF-. Neutrophils also release numerous toxic agents, e.g., proteases and reactive oxygen species, which contribute to the damage of lung tissue. If the consequences of the neutrophil-dominated inflammation in CF with an altered repair of the respiratory structures can be explained by an overwhelming neutrophil toxicity, the mechanisms leading to neutrophil accumulation and activation in the CF airways are poorly understood. One possibility is that pro-inflammatory and anti-inflammatory imbalance with excessive concentrations of the neutrophil chemotactic cytokine IL-8 certainly plays an important role in the influx of neutrophils in the inflamed airways. Locally, bacterial toxins and inflammatory mediators can directly activate the neutrophils to carry out their cytotoxic activities.

Another cause may be that in CF patients, impaired neutrophil functions may contribute to an abnormal release of inflammatory mediators. One recent research effort provided data suggesting that myeloperoxidase-dependent oxygenation activities are altered in blood neutrophils from CF heterozygotes and homozygotes.

A New Study

In considering a CF child’s airway, it is unclear whether the excessive presence of neutrophils is solely a consequence of an increased influx of these cells, or whether it is associated with a cellular dysfunction. Researchers from France studied the capacity of neutrophils to release the major neutrophil pro- and anti-inflammatory cytokines, respectively, IL-8 and IL-1-receptor antagonist (ra). They compared the production of these molecules by neutrophils isolated from the sputum and from the blood of children with CF. The capacity of neutrophils from CF children to release IL-8 and IL-1ra was also compared with cytokine production by blood neutrophils obtained from control subjects and by airway neutrophils obtained from children with chronic pulmonary disease related to dyskinetic cilia syndrome (chronic dilation of the bronchia). Finally, an assessment of the response of airways and blood neutrophils to the anti-inflammatory action of dexamethasone was performed.

The authors of “Distinct Cytokine Production by Lung and Blood Neutrophils from Children with Cystic Fibrosis” are Harriet Corvol, Katarina Chadelat, Jacky Jacquot, Olivier Tabary, Michele Boule’, and Annick Clement’, all from the Departement de Pneumologie Pediatrique-Institut National de la Santé et de la Recherche Médicale, Hopital Armand Trousseau; and Jean-Marc Cavaillon and Catherine Fitting, both from the Unite Postulante Cytokines and Inflammation, Institut Pasteur; all in Paris, France. Their findings appear in the June 2003 edition of the American Journal of Physiology – Lung Cellular and Molecular Physiology.


The CF population included 15 children, seven boys and eight girls (mean age: 12.6 ± 0.4 years). Cytokine production by blood neutrophils from CF patients was compared with control subjects, five healthy young adults (mean age: 30.8 ± 3.2 years) from the medical staff without history of lung disease and with normal lung function and four children, two boys and two girls (mean age: 11 ± 0.5 years) with dyskinetic cilia syndrome.

The experiment consisted of: (1) isolation of neutrophils in blood samples; (2) isolation of neutrophils in sputum samples; (3) neutrophil cultures analyzed with lipopolysaccharide (LPS); and (4) measurement of cytokine concentrations.


Key findings from this research showed that:

  • comparison of cytokine production by blood neutrophils from CF patients and from control subjects showed significantly increased IL-8 and decreased IL-1ra release by CF neutrophils;

  • comparison of cytokine production by airway and blood neutrophils from CF patients also documented distinct profiles: the spontaneous release of IL-8 and IL-1ra by airway neutrophils was significantly higher than that from blood neutrophils;

  • culture in the presence of LPS failed to further enhance cytokine production;

  • analysis of the effect of dexamethasone confirmed the difference in the responsiveness of lung and blood neutrophils in CF. Used at a concentration effective in reducing IL-8 production by blood neutrophils, dexamethasone (106 M) was unable to repress secretion of IL-8 by airway neutrophils.

  • In addition, comparison of cytokine production by airway neutrophils from children with CF and children with dyskinetic cilia syndrome also documented distinct profiles of secretion.


These results are consistent with a dysregulated cytokine production by lung and blood neutrophils in CF. They provide support to the hypothesis that not only the CF genotype but also the local environment may modify the functional properties of the neutrophils.

This study is the first report comparing airway and blood neutrophils from children with CF in terms of pro- and anti-inflammatory cytokine production and their respective responsiveness to glucocorticoids. Comparison of airway and blood neutrophils from the same CF patients showed distinct profiles of cytokine production spontaneously and in the presence of LPS, as well as differences in the response to dexamethasone, supporting the view that the local environment may modify the functional properties of the cells. In addition, comparisons of cytokine production by circulating neutrophils from children with CF and controls and by airway neutrophils from children with CF or dyskinetic cilia syndrome revealed significant differences, suggesting that genetic components may also participate in the altered neutrophil function in CF.

The findings provide additional evidence that the persistent and excessive inflammation in the lungs of CF patients involves a failure of the mechanisms that control the inflammatory response. An altered regulation of cytokine production by neutrophils is certainly an important factor that promotes continued inflammation and injury. Development of therapeutic interventions with specific cytokine inhibitors, anti-inflammatory cytokines, as well as anti-inflammatory drugs, which could target airway neutrophils, appears essential to control CF inflammation.

Donna Krupa | American Physiological Society
Further information:

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

New 4-D printer could reshape the world we live in

21.03.2018 | Life Sciences

Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

21.03.2018 | Trade Fair News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>