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Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia

¹ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA
² Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical School
³ Department of Radiology, University of Michigan Medical School
⁴ Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852-1448, USA
⁵ Mayo Clinic, Scottsdale, AZ 85259, USA
⁶ Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA

Correspondence to:
Dr C M Hogaboam
Department of Pathology, University of Michigan Medical School, Room 5214, Med Sci I, 1301 Catherine Road, Ann Arbor MI 48109–0602, USA; Hogaboam{at}med.umich.edu Background: Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs.

Aims: To examine the expression of interleukin 4 (IL-4), IL-13, and their corresponding receptor subunits in the various forms of IIP and normal patient groups.

Methods: Molecular and immunohistochemical analysis of IL-4, interferon (IFN), IL-13, IL-4 receptor (IL-R), and IL-13 receptor subunits in surgical lung biopsies (SLBs) from 39 patients (21 usual interstitial pneumonia (UIP), six non-specific interstitial pneumonia (NSIP), eight respiratory bronchiolitic interstitial lung disease (RBILD), and five normal controls).

Results: Molecular analysis demonstrated that IL-13R2, IL-13R1, and IL-4R were present in a greater proportion of upper and lower lobe biopsies from patients with UIP than patients with NSIP and RBILD. Immunohistochemical analysis of patients with UIP, NSIP, and RBILD revealed interstitial staining for all three receptor subunits, whereas such staining was only seen in mononuclear cells present in normal SLBs. Fibroblastic foci in patients with UIP strongly stained for IL-4R and IL-13R2. Localised expression of IL-4R was also seen in SLBs from patients with NSIP but not in other groups.

Conclusion: Some histological subtypes of IIP are associated with increased pulmonary expression of receptor subunits responsive to IL-4 and IL-13. These findings may be of particular importance in understanding the pathogenesis of IIP and, more importantly, may provide important novel therapeutic targets.

Keywords: interleukin 4; interleukin 13; interleukin 4 receptor; interleukin 13 receptor; idiopathic interstitial pneumonia

Abbreviations: ELISA, enzyme linked immunosorbent assay; FF, fibroblastic foci profusion; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HRCT, high resolution computed tomography; IFN, interferon ; IIP, idiopathic interstitial pneumonia; IL, interleukin; IL-4R, IL-4 receptor; IRAP, interleukin 1 receptor antagonist protein; NSIP, non-specific interstitial pneumonia; RBILD, respiratory bronchiolitic interstitial lung disease; RT-PCR, reverse transcription polymerase chain reaction; SLB, surgical lung biopsy; Th1, T helper type 1; UIP, usual interstitial pneumonia

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