The impact of cystic fibrosis on the immunologic profile of pediatric patients.

OBJECTIVE To compare the immunologic state of 44 pediatric patients with cystic fibrosis (CF) with a control group consisting of 16 healthy individuals. METHODS CF patients aged 3 to 12 years with moderate to good clinical score were selected for the study. Erythrocytic glutathione, production of reactive oxygen species, cytokines (TNF-a, IFN-g, IL-8, IL-6, IL-10) in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, serum concentrations of TGF-b2, IgA, IgG, IgM, IgE, and salivary IgA were evaluated. RESULTS The spontaneous production of TNF-a, IL-6, and IL-10, the PHA-stimulated production of IL-6, and the serum TGF-b2, IgA, and IgG were increased in samples from CF patients. Healthy subjects had a higher production of TNF-a in response to BCG. CONCLUSION Although CF patients appeared clinically stable, the results of their peripheral blood examinations demonstrated an impact on the immune system.

[1]  E. Beutler.  Red cell metabolism , 1971 .

[2]  W. Mosgoeller,et al.  Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation. , 1999, The European respiratory journal.

[3]  T. Noah,et al.  Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis. , 1997, The Journal of infectious diseases.

[4]  M. Lohmann‐Matthes,et al.  A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123. , 1990, Journal of immunological methods.

[5]  L. Lands,et al.  Lymphocyte glutathione levels in children with cystic fibrosis. , 1999, Chest.

[6]  M. Helbert,et al.  A simple flow cytometry assay using dihydrorhodamine for the measurement of the neutrophil respiratory burst in whole blood: comparison with the quantitative nitrobluetetrazolium test. , 1998, Journal of immunological methods.

[7]  M. Weinberger,et al.  The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis , 1995, Pediatric pulmonology.

[8]  Robert Horsburgh,et al.  An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. , 2007, American journal of respiratory and critical care medicine.

[9]  M. Konstan,et al.  Inflammatory cytokines in cystic fibrosis lungs. , 1995, American journal of respiratory and critical care medicine.

[10]  Freya Harrison,et al.  Microbial ecology of the cystic fibrosis lung. , 2007, Microbiology.

[11]  B. Wretlind,et al.  TNF-alpha and IL-8 in consecutive sputum samples from cystic fibrosis patients during antibiotic treatment. , 2000, Scandinavian journal of infectious diseases.

[12]  S. Freedman,et al.  Cystic fibrosis , 2009, The Lancet.

[13]  M. Cooper,et al.  THE IGA SYSTEM , 1966, The Journal of experimental medicine.

[14]  T. Ottenhoff.  New pathways of protective and pathological host defense to mycobacteria. , 2012, Trends in microbiology.

[15]  J. Freyssinet,et al.  Mechanisms of the noxious inflammatory cycle in cystic fibrosis , 2009, Respiratory research.

[16]  H. Forman,et al.  Abnormal glutathione transport in cystic fibrosis airway epithelia. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[17]  A. Clément,et al.  Oxidative stress induces extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase in cystic fibrosis lung epithelial cells: Potential mechanism for excessive IL-8 expression. , 2008, The international journal of biochemistry & cell biology.

[18]  W. Wheeler,et al.  Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study. , 1984, The Journal of pediatrics.

[19]  A. Pukhalsky,et al.  Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection. , 1999, Mediators of inflammation.

[20]  A. Prince,et al.  Cystic fibrosis: a mucosal immunodeficiency syndrome , 2012, Nature Medicine.

[21]  B. O'sullivan,et al.  Intensive Care Management of the Patient With Cystic Fibrosis , 2008, Journal of intensive care medicine.

[22]  I. Zipkin,et al.  Immunological studies of submaxillary saliva from patients with cystic fibrosis and from normal children. , 1968, The Journal of pediatrics.

[23]  S. Thorgeirsson,et al.  Transforming Growth Factor-β1 in Plasma and Liver of Children with Liver Disease , 1998, Pediatric Research.

[24]  G. Pier.  The challenges and promises of new therapies for cystic fibrosis , 2012, The Journal of experimental medicine.

[25]  M. Kemna,et al.  Reduced IL‐10 secretion by CD4+ T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR) , 1996, Clinical and experimental immunology.

[26]  A. Kharazmi,et al.  The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type , 2000, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[27]  J. Elborn,et al.  Circulating immunoreactive interleukin-6 in cystic fibrosis. , 1998, American journal of respiratory and critical care medicine.

[28]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[29]  G. Biberfeld,et al.  A new method for measuring lymphoproliferation at the single-cell level in whole blood cultures by flow cytometry. , 1996, Journal of immunological methods.

[30]  D. Norman,et al.  Plasma tumour necrosis factor alpha in cystic fibrosis. , 1991, Thorax.

[31]  Patrick Kim Chiaw,et al.  Molecular basis for the ATPase activity of CFTR. , 2008, Archives of biochemistry and biophysics.

[32]  R. Geha,et al.  Hypogammaglobulinemia in patients with cystic fibrosis. , 1980, The New England journal of medicine.

[33]  J. Cavaillon,et al.  Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease. , 1999, The European respiratory journal.

[34]  M. Berger,et al.  Chronic Inflammation in the Cystic Fibrosis Lung: Alterations in Inter- and Intracellular Signaling , 2008, Clinical reviews in allergy & immunology.

[35]  S. Fiel,et al.  Erythrocytic glutathione in cystic fibrosis. A possible marker of pulmonary dysfunction. , 1994, Chest.

[36]  W. Warwick,et al.  The IgA system. 3. IgA levels in the serum and saliva of pediatric patients--evidence for a local immunological system. , 1967, The Journal of pediatrics.

[37]  M. Hodson,et al.  Serum immunoglobulins and immunoglobulin G subclasses in cystic fibrosis related to the clinical state of the patient. , 1988, The European respiratory journal.