Bolus infusion of human urinary trypsin inhibitor improves intractable interstitial pneumonia in patients with connective tissue diseases.
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 10(5) 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, PaO(2) 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-beta1, 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 10(5) 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-beta1 concentrations were higher in the patients than in normal subjects, and infusion of 3 x 10(5) U of UT reduced the concentrations within 3 h of infusion.


CONCLUSIONS
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.
Tsujimura
S
S
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan.
Saito
K
K
Nakayamada
S
S
Tanaka
Y
Y
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003240:Connective Tissue Diseases / Q000150:complications*; D004341:Drug Evaluation; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D053773:Transforming Growth Factor beta1 / Q000097:blood; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000097:blood / Q000627:therapeutic use*
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006023:Glycoproteins; D053773:Transforming Growth Factor beta1; D014361:Trypsin Inhibitors; C028665:urinastatin