title: Effects of treatment in the levels of circulating cytokines and growth factors in cystic fibrosis and dialyzed patients by multi-analytical determination with a biochip array platform.
abstract: Chronic inflammatory diseases need non-invasive sensitive, reliable and predictive clinical biomarkers for diagnosis and monitoring therapy. Since inflammation is a complex phenomenon, simultaneous evaluation of different analytes in the same sample may help in defining this complexity and in developing specific anti-inflammatory intervention strategies. In this study, we used a biochip array system capable of measuring 12 cytokines and growth factors (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1 α, IL-1 β, IFN-γ, TNF-α, MCP-1, VEGF, and EGF) in three groups: 97 control subjects; 24 cystic fibrosis (CF) patients before and during the antibiotic treatment (6 and 15days) for acute pulmonary exacerbation as well as 15days after the withdrawal of therapy; 22 children and young adults on chronic hemodialysis (HD) at the beginning and at the end of a standard HD session. CF patients in acute exacerbation displayed higher IL-2, IL-6, VEGF and MCP-1 levels than the control subjects. IL-6 significantly decreased during therapy (P<0.01) but not 15days after the withdrawal of therapy. IL-8 and EGF levels were significantly lower after 15days from the interruption of therapy (P<0.05 and P<0.01 respectively). Regression analysis showed that IL-4 and IL-6 correlated with the amelioration of the respiratory function during therapy. Patients on HD displayed higher IL-6 but lower IL-2, IL-4, IL-8, IFN-γ and EGF levels than control subjects. Serum levels of IL-8, IL-10 and IFN-γ were significantly higher at the end of the HD session (P<0.05 for all three). A biochip array allowed to define a pattern of cytokines/growth factors associated with an acute exacerbation in CF patients and IL-4 and IL-6 as predictors of response to therapy. In younger HD patients, we identified a biomarker pattern which is different from that of older patients. Finally, further studies are warranted to examine the role of these biomarkers in the pathogenesis of complications in HD patients.
authors.affiliation: Laboratory of Clinical Pathology and CF Microbiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Amedea Silvia
authors.initials: AS
authors.lastname: Tirelli
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.forename: Erminio
authors.initials: E
authors.lastname: Torresani
authors.forename: Francesca
authors.initials: F
authors.lastname: Fortunato
authors.forename: Arianna
authors.initials: A
authors.lastname: Biffi
authors.forename: Lisa
authors.initials: L
authors.lastname: Cariani
authors.forename: Valeria
authors.initials: V
authors.lastname: Daccò
authors.forename: Annalucia
authors.initials: A
authors.lastname: Carbone
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Fabio
authors.initials: F
authors.lastname: Paglialonga
authors.forename: Massimo
authors.initials: M
authors.lastname: Conese
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000097:blood* / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D012044:Regression Analysis; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D002097:C-Reactive Protein