PT  - JOURNAL ARTICLE
AU  - Inga Wessels
AU  - Johanna Theresa Pupke
AU  - Klaus-Thilo von Trotha
AU  - Alexander Gombert
AU  - Anika Himmelsbach
AU  - Henrike Josephine Fischer
AU  - Michael J Jacobs
AU  - Lothar Rink
AU  - Jochen Grommes
TI  - Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity
AID  - 10.1136/thoraxjnl-2019-213357
DP  - 2020 Mar 01
TA  - Thorax
PG  - 253--261
VI  - 75
IP  - 3
4099  - http://thorax.bmj.com/content/75/3/253.short
4100  - http://thorax.bmj.com/content/75/3/253.full
SO  - Thorax2020 Mar 01; 75
AB  - Introduction Zinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested.Methods 64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well.Results Injecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail.Conclusion Zinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.