Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis

Robert M. Strieter, Karen M. Starko, Richard I. Enelow, Imre Noth, Vincent C. Valentine, K. Brown, A. Frost, L. Lancaster, P. Noble, A. Chan, Marilyn K Glassberg Csete, M. Kallay, P. Economou, S. Sahn, M. Wencel, D. A. Zisman, W. Bradford, M. Burdick, M. P. Keane, T. Ganz

Research output: Contribution to journalArticle

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Abstract

In a recent study of IFN-γ 1b in 330 patients with idiopathic pulmonary fibrosis (IPF), progression-free survival was unchanged; however, a trend toward lower mortality was seen in IFN-γ 1b-treated patients compared with placebo-treated patients (9.9 vs. 16.7%; p = 0.08). The purpose of this randomized, double-blind, placebo-controlled trial was to characterize molecular effects of subcutaneous IFN-γ 1b (200 μg) thrice weekly for 6 months versus placebo in 32 patients with IPF. Messenger RNA in transbronchial lung biopsies and bronchoalveolar lavage cell pellet and protein levels in bronchoalveolar lavage fluid (BALF) and plasma were evaluated. After IFN-γ 1b treatment, IFN-inducible T cell-α chemoattractant/CXCL11 (a chemokine with immunomodulatory, antiangiogenic, and defensin-like antimicrobial properties) increased in BALF (p = 0.016) and plasma (p < 0.001); BALF levels of epithelial neutrophil-activating protein-78/CXCL5 (p = 0.054), platelet-derived growth factor A (p = 0.033), and Type I procollagen (p = 0.096) were lower; and IFN-γ levels were higher (p = 0.093) versus placebo. For messenger RNA in transbronchial biopsies, trends (p > 0.05 and ≤ 0.10) associated with IFN-γ 1b treatment included an increase in IFN-inducible T cell-α chemoattractant/CXCL11, a decrease in elastin, and smaller increases for Type III procollagen and platelet-derived growth factor B. Changes in biomarkers of fibrosis, angiogenesis, proliferation, immunomodulation, and antimicrobial activity suggest that IFN-γ 1b may affect IPF through multiple pathways.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume170
Issue number2
StatePublished - Jul 15 2004

Fingerprint

Idiopathic Pulmonary Fibrosis
Interferons
Biomarkers
Chemotactic Factors
Placebos
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Chemokine CXCL11
Proto-Oncogene Proteins c-sis
Defensins
T-Lymphocytes
Collagen Type III
Immunomodulation
Elastin
Disease-Free Survival
Fibrosis
Biopsy
Messenger RNA
Mortality
Therapeutics

Keywords

  • 1b
  • IFN-γ
  • Proteins
  • Pulmonary fibrosis
  • RNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Strieter, R. M., Starko, K. M., Enelow, R. I., Noth, I., Valentine, V. C., Brown, K., ... Ganz, T. (2004). Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 170(2), 133-140.

Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis. / Strieter, Robert M.; Starko, Karen M.; Enelow, Richard I.; Noth, Imre; Valentine, Vincent C.; Brown, K.; Frost, A.; Lancaster, L.; Noble, P.; Chan, A.; Glassberg Csete, Marilyn K; Kallay, M.; Economou, P.; Sahn, S.; Wencel, M.; Zisman, D. A.; Bradford, W.; Burdick, M.; Keane, M. P.; Ganz, T.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 170, No. 2, 15.07.2004, p. 133-140.

Research output: Contribution to journalArticle

Strieter, RM, Starko, KM, Enelow, RI, Noth, I, Valentine, VC, Brown, K, Frost, A, Lancaster, L, Noble, P, Chan, A, Glassberg Csete, MK, Kallay, M, Economou, P, Sahn, S, Wencel, M, Zisman, DA, Bradford, W, Burdick, M, Keane, MP & Ganz, T 2004, 'Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis', American Journal of Respiratory and Critical Care Medicine, vol. 170, no. 2, pp. 133-140.
Strieter, Robert M. ; Starko, Karen M. ; Enelow, Richard I. ; Noth, Imre ; Valentine, Vincent C. ; Brown, K. ; Frost, A. ; Lancaster, L. ; Noble, P. ; Chan, A. ; Glassberg Csete, Marilyn K ; Kallay, M. ; Economou, P. ; Sahn, S. ; Wencel, M. ; Zisman, D. A. ; Bradford, W. ; Burdick, M. ; Keane, M. P. ; Ganz, T. / Effects of interferon-γ 1b on biomarker expression in patients with idiopathic pulmonary fibrosis. In: American Journal of Respiratory and Critical Care Medicine. 2004 ; Vol. 170, No. 2. pp. 133-140.
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