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The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency

Authors Schmid ST, Koepke J, Dresel M, Hattesohl A, Frenzel E, Perez J, Lomas DA, Miranda E, Greulich T, Noeske S, Wencker M, Teschler H, Vogelmeier C, Janciauskiene S, Koczulla AR

Received 1 June 2012

Accepted for publication 23 July 2012

Published 28 September 2012 Volume 2012:7 Pages 687—696


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

ST Schmid,1 J Koepke,1 M Dresel,1 A Hattesohl,1 E Frenzel,2 J Perez,3 DA Lomas,4 E Miranda,5 T Greulich,1 S Noeske,1 M Wencker,6 H Teschler,6 C Vogelmeier,1 S Janciauskiene,2,* AR Koczulla1,*

1Department of Internal Medicine, Division for Pulmonary Diseases, University Hospital Marburg, Marburg, Germany; 2Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 3Department of Cellular Biology, University of Malaga, Malaga, Spain; 4Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 5Department of Biology and Biotechnology, Istituto Pasteur – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy; 6Department of Pneumology, West German Lung Clinic, Essen University Hospital, Essen, Germany

*These authors contributed equally to this work

Background: The major concept behind augmentation therapy with human α1-antitrypsin (AAT) is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys)-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema.
Objective: To evaluate the short-term effects of augmentation therapy (Prolastin®) on plasma levels of AAT, C-reactive protein, and chemokines/cytokines.
Materials and methods: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12) on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8), monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL).
Results: There were significant fluctuations in serum (but not in exhaled breath condensate) levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor- α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells.
Conclusion: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.

Keywords: Prolastin, augmentation therapy, cytokines, IL-8, exhaled breath condensate, neutrophils

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