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.