DR Smith, SL Kunkel, TJ Standiford, MW Rolfe, JP Lynch 3rd, DA Arenberg, CA Wilke, MD Burdick, FJ Martinez and JN Hampton
Department of Medicine, University of Michigan Medical School, Ann Arbor, USA.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood interstitial disease that usually proves refractory to therapy and results in irreversible tissue scarring and pulmonary dysfunction. Previous investigations have suggested a number of possible mediators of inflammation and fibrosis that typify IPF. We report increases in lung interleukin-1 receptor antagonist protein (IRAP) content in patients with IPF, as compared with normal control subjects. Importantly, this increase in IRAP was not accompanied by concomitant increases in interleukin-1 beta (IL-1 beta), resulting in a local environment that may be profibrotic. Tissue homogenates and bronchoalveolar lavage fluid from patients with IPF both demonstrate elevated IRAP content compared with that in normal subjects. Immunohistochemical staining and in situ hybridization localize IRAP to hyperplastic type II pneumocytes, macrophages, and local stromal cells. Finally, in vitro studies utilizing fibroblasts isolated from patients with IPF demonstrated no difference in constitutive IRAP production compared with that in normal subjects, but they revealed an exaggerated response to stimulation with transforming growth factor-beta (TGF-beta). These findings suggest that the fibrotic tissue changes of IPF and possibly other chronic interstitial lung diseases may result in part from the local effects of IRAP, and they also demonstrate that pulmonary nonimmune cells may influence local tissue changes through the elaboration of IRAP.

This article has been cited by other articles:

				C Jakubzick, E S Choi, S L Kunkel, H Evanoff, F J Martinez, R K Puri, K R Flaherty, G B Toews, T V Colby, E A Kazerooni, et al. Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia J. Clin. Pathol., May 1, 2004; 57(5): 477 - 486. [Abstract] [Full Text] [PDF]

				R. M. Strieter Mechanisms of Pulmonary Fibrosis : Conference Summary Chest, July 1, 2001; 120(2007): 77S - 85S. [Full Text] [PDF]

				M. WHYTE, R. HUBBARD, R. MELICONI, M. WHIDBORNE, V. EATON, C. BINGLE, J. TIMMS, G. DUFF, A. FACCHINI, A. PACILLI, et al. Increased Risk of Fibrosing Alveolitis Associated with Interleukin-1 Receptor Antagonist and Tumor Necrosis Factor-alpha Gene Polymorphisms Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 755 - 758. [Abstract] [Full Text] [PDF]

				M. Malyak, J. M. Guthridge, K. R. Hance, S. K. Dower, J. H. Freed, and W. P. Arend Characterization of a Low Molecular Weight Isoform of IL-1 Receptor Antagonist J. Immunol., August 15, 1998; 161(4): 1997 - 2003. [Abstract] [Full Text] [PDF]

				M. Malyak, M. F. Smith Jr., A. A. Abel, K. R. Hance, and W. P. Arend The Differential Production of Three Forms of IL-1 Receptor Antagonist by Human Neutrophils and Monocytes J. Immunol., August 15, 1998; 161(4): 2004 - 2010. [Abstract] [Full Text] [PDF]