Analysis of cytokine dynamics in corneal allograft rejection

Motivated by the discovery of oscillations in tumour necrosis factor-α (TNF-α) concentration in the aqueous humour of rabbits undergoing corneal allograft rejection, a simple mathematical model is developed for the regulation of TNF-α, which incorporates both negative feedback and amplification path...

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Bibliographic Details
Published in:Proceedings of the Royal Society. B, Biological sciences Biological sciences, 1999-11, Vol.266 (1434), p.2217-2223
Main Authors: Chan, Cliburn C. W., Stark, Jaroslav, George, Andrew J. T.
Format: Article
Language:English
Subjects:
Animals
Antigens
Corneal Transplantation
Corneal Transplantation - immunology
Cytokine Network
Cytokines
Dose response relationship
Graft rejection
Graft Rejection - immunology
Hysteresis
Mathematical Model
Mathematical models
Mental stimulation
Modeling
Models, Immunological
Models, Theoretical
Nonlinear Dynamics
Oscillation
Oscillations
Positive feedback
Rabbits
Time Factors
Transplantation, Homologous
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - physiology
Tumour Necrosis Factor-Α
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Summary:Motivated by the discovery of oscillations in tumour necrosis factor-α (TNF-α) concentration in the aqueous humour of rabbits undergoing corneal allograft rejection, a simple mathematical model is developed for the regulation of TNF-α, which incorporates both negative feedback and amplification pathways. Mathematical analysis reveals a surprisingly rich behavioural repertoire for this simple cytokine pathway, including excitability, threshold behaviour, hysteresis, oscillations and bistability. This suggests new possibilities for experimental demonstration, and reveals the potential contributions of nonlinear dynamics to understanding cytokine regulation.
ISSN:0962-8452
1471-2954
DOI:10.1098/rspb.1999.0911