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Int J Chron Obstruct Pulmon Dis. 2012;7:687-96. doi: 10.2147/COPD.S34560. Epub 2012 Sep 28.

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

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1
Department of Internal Medicine, Division for Pulmonary Diseases, University Hospital Marburg, Marburg, Germany.

Abstract

BACKGROUND:

The major concept behind augmentation therapy with human α(1)-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:

IL-8; Prolastin; augmentation therapy; cytokines; exhaled breath condensate; neutrophils

PMID:
23055718
PMCID:
PMC3468059
DOI:
10.2147/COPD.S34560
[Indexed for MEDLINE]
Free PMC Article
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