PURPOSE:Th2 and Th1 cytokines are involved in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) and Organizing Pneumonia (OP), respectively. The aim of this study was to evaluate by flow cytometry, rather than Enzyme-Linked ImmunoSorbent Assay (ELISA) routinely performed, the expression of these cytokines in Bronchoalveolar Lavage (BAL) of these patients and their correlation with clinical markers.
METHODS:The study prospectively evaluated BAL titers of IL-1β, IL-6, IL-8, IL-10, IL-12 and TNF-α in seventeen patients with IPF (group A, n=11) and OP (group B, n=6). Control group consisted of five healthy volunteers. Diagnosis of IPF was made by lung biopsy or ATS/ERS criteria. Diagnosis of Organizing Pneumonia was based on lung biopsy. BAL extracellular cytokines were measured by a Cytometric Bead Array assay (CBA) by Beckton-Dickinson. Results were compared between groups A, B and controls and correlated with BAL‘s absolute neutrophils and lymphocytes, age and the Composite Physiologic Index (CPI).
RESULTS:IL-6, IL-8, IL-1β and IL-10 were found significantly elevated in group A compared to controls (p <0,05). TNF-α and IL-12 were significantly elevated in group B compared to controls (p <0,05). Group A exhibited statistically marked elevation of IL-6, IL-8, IL-1β and IL-10 compared to group B (p <0,05). In group B, IL-12 was also significantly elevated compared to group A (p <0,05). Absolute BAL neutrophil counts in group A correlated positively with IL-10 (p<0,05), while absolute BAL lymphocytes in group B were inversely correlated with IL-1β (p<0,05). Correlation with age or CPI (in group A) was not significant.
CONCLUSION:Results are similar to studies using ELISA. Activation inducing cytokines and IL-10 in IPF patients promote anti-Th1 activity and neutrophils accumulation. Balance of anti-fibrotic (IL-12) to anti-inflammatory (IL-10) cytokines is down-regulated. In OP patients, IL-12 and Th1 pathway prevail.
CLINICAL IMPLICATIONS:Apart from Cluster Designation (CD) assignment, BAL flow cytometry may provide through soluble cytokines clinical clues to diagnosis. Balance between protective, acute phase and fibrotic cytokines may help to explain different clinical manifestations.
DISCLOSURE:Ilias Papanikolaou, No Financial Disclosure Information; No Product/Research Disclosure Information