Tissue Damage & Cytotoxicity
The contemporary theory of the immune response states that the immune system is not programmed to respond to foreign particles, as it was conceived for many years during the self-nonself era of immunology. What turns the immune system on and off is a very important question in understanding disease and pathology. The condition of the tissue is very central to understanding homeostasis, tolerance and the immune response. The central dogma of immunology is that the immune system receives signals to respond from the ‘tissue’ and that the immune system is far less concerned with things that are foreign than with those that do damage.
Understand tissue damage as the central driver of an immune response and the impact on modelling,
We emphasise on tissue damage as it is the central driver of an immune response whether the damage is an outcome of a drug molecule or a pathogen or endogenous metabolites. The prediction of a drug molecule’s immunogenicity or cytotoxicity to non-target tissue will be best understood at this upstream event.
We have found, from in vitro human studies, certain popular drugs to cause direct damage to certain tissue types, for example amiodarone and azithromycin will affect human lung cells (A549 cells).
Why focus on tissue damage?
Tissue damage that is non-lethal/non-toxic will generate an immune response that may lead to autoimmune pathogenesis. The immune system is programmed to respond to distressed tissue that is associated with an altered microenvironment (protein expression) and is typically followed by inflammation.
Any drug has the potential to cause unwanted tissue damage. The outcome of such damage is the release of intracellular molecules to the immune system. Conventional ‘immunogenicity’ testing considerations are limited to ‘antigenicity’ testing of the drug molecule only. In standard toxicology studies, immune response data such as infiltrations of lymphocytes in tissue sites are ignored as transient immunity and the possibility of disease occurring from chronic immunogenic events is overlooked. It is this broader immunogenicity of a drug that we consider serious and our assays are designed to answer your questions about drug-induced tissue damage and immune response.
Tissue Damage Study involves:
- In vitro cell systems representing human tissues of drug target sites
- Drug challenge
- Assessment of cell damage and cytotoxicity
- Assessment of immunogenic by-products of tissue damage
How Will You Benefit?
- Determine drug induced damage to non-target tissue
- Better understand the potential of a drug molecule’s immunogenicity or cytotoxicity to non-target tissue at this upstream event
- Predict drug-induced secondary pathology
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