Modelling the dynamics of TNF-alpha
- Student: Jason Zhen
- Program: Bachelor Biomedical Sciences
- Periode: October 2021 – February 2022
- Supervisor: Antoine van Kampen
Tumor Necrosis Factor (TNF) is a cytokine, which is primarily produced by macrophages, and a key factor in patients of inflammatory autoimmune diseases. In recent years, development TNF inhibitors (TNFi), such as Adalimumab, has lead to significantly improved treatment of rheumatoid arthritis (RA) cases by suppressing TNF and other pro-inflammatory cytokines (Ternant et al., 2015; Willrich et al., 2015). Although past empirical evidence showed that TNFi’s are able to neutralize TNF, the exact underlying mechanisms remain unknown. Interestingly, a recent study by Berkhout et al. (2019) presented increasing levels of TNF when treating RA patients with Adalimumab, which is counter-intuitive given the mode of action of TNFi. Most likely, not TNF was measured but the complex of TNF and TNFi.
- Berkhout, L. C., l’ Ami, M. J., Ruwaard, J., Hart, M. H., Heer, P. O., Bloem, K., … Rispens, T. (2019). Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay. Science Translational Medicine, 11(477), eaat3356.
- Ternant, D., Ducourau, E., Fuzibet, P., Vignault, C., Watier, H., Lequerré, T., … Paintaud, G. (2015). Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis. British Journal of Clinical Pharmacology, 79(2), 286–297.
- Willrich, M. A. V., Murray, D. L., & Snyder, M. R. (2015). Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Translational Research, 165(2), 270–282.
The aim of this project is to construct a computational model based on ordinary differential equations to investigate dynamics of TNF-alpha and TNFi. In particular we will address the following questions:
- Does TNF increase upon treatment with TNFi?
- What is the minimum concentration of TNFi to neutralize all TNF in a patient?
- How do small changes in TNF concentration affect the concentration of the TNF-TNFi complex?
The computational model will be developed in a Python notebook.
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