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. © 2012 Schmid et al, publisher and licensee Dove Medical Press Ltd.
CITATION STYLE
Schmid, S. T., Koepke, J., Dresel, M., Hattesohl, A., Frenzel, E., Perez, J., … Koczulla, A. R. (2012). The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency. International Journal of COPD, 7, 687–696. https://doi.org/10.2147/COPD.S34560
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