Phd in EXPERIMENTAL MEDICINE

Thesis title: Profili citochinici associati all’outcome nella fibrosi polmonare idiopatica

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease characterized by a progressive course and heterogeneous prognosis. Clinical, functional, and radiological tools are essential for patient assessment; however, they do not always fully capture the biological complexity of the disease or accurately predict its progression. This study exploratively assessed the association between circulating cytokine and chemokine profiles and clinical outcomes in patients with IPF. Within a clinical cohort of patients with fibrosing interstitial lung disease, clinical and functional data and plasma samples were collected and subsequently organized into a structured database and biobank. The translational analysis was conducted in 29 patients with IPF using the Bio-Plex 40-plex and Olink Target 48 Cytokine multiplex platforms, with particular focus on 24-month mortality. The results revealed marked heterogeneity in molecular profiles and identified several signals associated with an unfavorable prognosis. In particular, CCL8, CXCL12, CCL2, IL-6, and CCL3 showed a consistent pattern across the two analytical platforms. Survival analyses also suggested reduced survival in patients with higher levels of CCL8 and CXCL12, with a similar trend observed for CCL2. Although no validated biomarkers or immediately applicable therapeutic targets were identified, the study suggests the existence of a potential immunofibrotic profile associated with unfavorable outcomes in IPF. These findings, which require confirmation in larger cohorts and prospective studies, highlight the potential value of cytokine and chemokine profiling as a complementary tool for improving the understanding of disease heterogeneity and guiding future translational research strategies.