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Rheumatology Advance Access originally published online on April 14, 2008
Rheumatology 2008 47(6):907-913; doi:10.1093/rheumatology/ken067
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Bolus infusion of human urinary trypsin inhibitor improves intractable interstitial pneumonia in patients with connective tissue diseases

S. Tsujimura, K. Saito, S. Nakayamada and Y. Tanaka

First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.

Correspondence to: Y. Tanaka, First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan. E-mail: tanaka{at}med.uoeh-u.ac.jp


  Abstract

Objective. Interstitial pneumonia (IP) associated with CTDs often progresses despite conventional immunosuppressive treatment. We investigated the efficacy of human urinary trypsin (UT) inhibitor (ulinastatin) on refractory IP.

Methods. Five patients with IP received UT inhibitor (3 x 105 U) infusion into the internal jugular vein, three times in a single day. The response to this therapy was assessed clinically and by chest CT, PaO2 and serum KL-6. The kinetics of UT inhibitor was determined in arterial blood. We measured serum levels of monocyte chemotactic protein-1 and TGF-β1, which are thought to be involved in the pathogenesis of IP.

Results. Serum concentrations of UT inhibitor increased immediately to >150 U/ml after infusion of 3 x 105 U of UT inhibitor. The treatment resulted in clinical and radiological improvements in four patients, and allowed reduction of oxygen therapy following improvement of hypoxaemia within 1 month. UT inhibitor decreased serum levels of KL-6 in all patients and had no adverse effects. MCP-1 and TGF-β1 concentrations were higher in the patients than in normal subjects, and infusion of 3 x 105 U of UT reduced the concentrations within 3 h of infusion.

Conclusion. UT inhibitor bolus infusion therapy is a potentially useful therapeutic strategy for intractable IP based on the different mechanism of action relative to conventional immunosuppressive therapy and lack of serious treatment-related adverse effects.

KEY WORDS: Human urinary trypsin inhibitor, Interstitial pneumonia, Connective tissue diseases

Submitted 22 October 2007; revised version accepted 29 January 2008.
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