Journal article

Publication year: 2021

Journal: Pulmonary Pharmacology and Therapeutics

Volume number: 68

ISSN: 1094-5539

DOI Link: https://doi.org/10.1016/j.pupt.2021.102020

Publisher: Elsevier

Abstract: 
The acute phase protein alpha 1-antitrypsin (AAT) inhibits numerous proteases, specifically neutrophil elastase. Patients with an AAT deficiency due to mutations frequently develop early onset emphysema. The commercial preparations of human plasma AAT are clinically used as biopharmaceuticals to protect the lung tissue of AAT-deficient patients from damage caused by neutrophil elastase. Accordingly, preparations of AAT are validated for their anti-elastase activity. However, several anti-inflammatory effects of AAT were described, some of them being independent from its anti-protease function. We recently demonstrated that AAT isolated from the blood of healthy persons efficiently inhibits the ATP-induced release of interleukin-1 beta by human monocytes. This finding is of therapeutic relevance, because IL-1 beta plays an important role in numerous debilitating and life-threatening inflammatory diseases. As anti-inflammatory functions of AAT are of increasing clinical interest, we compared the potential of two widely used AAT preparations, Prolastin (R) and Respreeza (R), to inhibit the ATP-induced release of IL-1 beta using human monocytic U937 cells. We detected marked functional differences between both medicaments. The AAT preparation Respreeza (R) is less active compared to Prolastin (R) regarding the inhibition of the ATP-induced release of monocytic IL-1 beta. Chemical oxidation of Respreeza (R) restored this anti-inflammatory activity, while destroying its anti-protease function. Our data suggest that the anti-inflammatory potential and the anti-protease function of AAT can be fully uncoupled. In the light of the increasing clinical interest in antiinflammatory functions of AAT, commercial AAT preparations should be carefully reinvestigated and optimized to preserve the dual anti-protease and anti-inflammatory activity of native AAT.

Harvard Citation style: Agne, A., Richter, K., Padberg, W., Janciauskiene, S. and Grau, V. (2021) Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β, Pulmonary Pharmacology and Therapeutics, 68, Article 102020. https://doi.org/10.1016/j.pupt.2021.102020

APA Citation style: Agne, A., Richter, K., Padberg, W., Janciauskiene, S., & Grau, V. (2021). Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β. Pulmonary Pharmacology and Therapeutics. 68, Article 102020. https://doi.org/10.1016/j.pupt.2021.102020