Case Study:
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.
d0
d1
d4
Amiodarone effect on immunomodulation
Ciprofloxacin ug/ml
Paracetamol uM
Azithromycin ug/ml
Problem:
Can we assess tissue damage caused by commonly used drugs and if such damage is immunogenic?
Approach:
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.
Findings:
Amiodarone and azithromycin were damaging to lung cells, which were also stimulatory for dendritic cells.
