Tissue Damage & Cytotoxicity
What was the challenge?
A drug may cause unwanted damage to target or non-target tissue. A drug may also be cytotoxic to target or non-target cells at certain doses. Tissue damage or cytotoxicity is a major driver immune response. While cytotoxicity is an important concern in drug validation, tissue damage on a chronic basis that can generate immune driven organ specific or systemic conditions should also be a concern in drug research. There are many known immune-mediated diseases that are caused by chronic drug treatment, for example, interstitial lung disease caused by amiodarone.
Can we assess tissue damage caused by commonly used drugs and if such damage is immunogenic?
Considering lung cells as one of the most vascular cells that are frequently exposed to drugs and immunogens we modelled an A549 tissue system for drug-induced damage experiment. A549 lung cells were challenged with amiodarone, azithromycin, paracetamol and ciprofloxacin and tested for cell death and imuunomodulatory effects.
Amiodarone and azithromycin were damaging to lung cells, which were also stimulatory for dendritic cells.