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2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Th2 Products IL-4 and IL-13 are Associated with Rapidly Progressive Idiopathic
Pulmonary Fibrosis
Presenter: Richard H. Huynh
Division: Pulmonary & Critical Care Medicine
☐Faculty ☒Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: S Weigt, JA Belperio
Co-Investigators: MY Shino, A Derhovanessian, DM
Sayah, R Saggar, V Palchevskiy, A Ardehali, DJ Ross, JP Lynch, M Keane
Thematic Poster Category: Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Atherosclerosis
Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia
characterized by a histologic pattern of usual interstitial pneumonia (UIP). IPF disease progression is
highly variable and several clinical courses have been theorized as distinct IPF phenotypes including:
slowly progressive disease, rapidly progressive, and relatively stable with periods of acute decline.
Gene expression profiles between patients with stable disease and those with rapid progression have
been found to be different. The T helper cell 2 (Th2) cytokine milieu, in particular interleukin-4 (IL-4)
and interleukin-13 (IL-13), has been implicated in the pathogenesis of pulmonary fibrosis. We aim to
compare IL-4 and IL-13 expression in the lung at the protein level from IPF patients with rapidly
progressive disease versus those with stable pulmonary function.
Methods: Lung parenchyma was collected at the time of lung transplantation from 89 patients
diagnosed with IPF. Protein concentrations of IL-4 and IL-13 in the lung parenchyma were quantified
by multiplex bead-based sandwich immunoassay (Luminex). Retrospectively patients were
characterized as rapidly progressive (N=56) or stable (N=14) disease, based on forced vital capacity
(FVC) and diffusion capacity for carbon monoxide (DLco) data collected in the 1-year preceding lung
transplantation. Rapid progression was defined as a 10% reduction in FVC and/or a 15% reduction in
DLco. Patients with incomplete FVC or DLco data were excluded (N=19). Non-parametric statistical
analysis was performed via Kruskal-Wallis testing between the two groups. Categorical data analysis
was performed via Chi-squared testing between the two groups.
Results: The baseline clinical characteristics of the patients characterized as rapidly progressive and
slowly progressive IPF were similar including age and sex. Median concentrations of IL-4 in the
explanted lung parenchyma of patients characterized as rapidly progressive were significantly elevated
as compared to stable IPF patients (6.345 pg/mL vs. 2.36 pg/mL, p = 0.04). Similarly, a greater
percentage of patients characterized as rapidly progressive had detectable concentrations of IL-13 as
compared to patients characterized as slowly progressive (53.57% versus 14.29%, p = 0.0055).
Conclusion:
Elevated concentrations of the Th2 products IL-4 and IL-13 in the lung was associated with rapidly
progressive IPF. Prospective investigations regarding Th2 associated protein levels and the
relationship with disease phenotype are warranted in order to determine the prognostic significance
and better elucidate disease pathogenesis.
Figures:
Figure 1: IL-4 Protein Concentrations in Lung Tissue
Figure 2: IL-13 Protein Concentrations in Lung Tissue