Clinical Outcomes Associated with Interleukin 6 and Interleukin 8 Cytokine Production in Cystic Fibrosis

Abstract

Background: Cystic fibrosis (CF) clinical outcomes remain difficult to prognosticate. Elevated cytokine profiles in vivo are associated with obstructive lung diseases including CF. However, no studies to date have conducted a longitudinal clinical outcome analysis of early cytokine response on CF. Materials: To assess high risk cystic fibrosis (CF) clinical outcomes based on peripheral blood mononuclear cell (PBMC) in vitro cytokine response to Pseudomonas auruginosa antigen. Methods: PBMCs were stimulated with Pseudomonas aeruginosa antigen. Resultant cytokines TNF-alpha, IL-6 and IL-8 were measured by ELISA. PBMC cytokine response was characterized as high and low production of cytokines. Each group was analyzed for subsequent clinical outcomes including pulmonary function and rates of hospitalization. Results: Low and high level TNF-alpha and IL-6 groups lung function rate of decline did not show any remarkable difference. Between the groups with low and high levels of IL-8, there was a significant difference in rates of decline of FVC and FEV-1, with a greater decline in the high IL-8 producing group than the low IL-8 group. Conclusion: Stimulated cytokine production in vitro was associated with specific long-term clinical outcomes of CF patients. Specifically, elevated IL-8 production after Pseudomonas aeruginosa stimulation correlated with decline in lung function and hospitalization rate over 14 years of clinical follow up. This approach may potentially limit cytokine impact on pulmonary disease burden.