Optimal control of innate immune response

Robert F. Stengel, Raffaele Ghigliazza, Nilesh Kulkarni, Olivier Laplace

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Treatment of a pathogenic disease process is interpreted as the optimal control of a dynamic system. Evolution of the disease is characterized by a non-linear, fourth-order ordinary differential equation that describes concentrations of pathogens, plasma cells, and antibodies, as well as a numerical indication of patient health. Without control, the dynamic model evidences sub-clinical or clinical decay, chronic stabilization, or unrestrained lethal growth of the pathogen, depending on the initial conditions for the infection. The dynamic equations are controlled by therapeutic agents that affect the rate of change of system variables. Control histories that minimize a quadratic cost function are generated by numerical optimization over a fixed time interval, given otherwise lethal initial conditions. Tradeoffs between cost function weighting of pathogens, organ health, and use of therapeutics are evaluated. Optimal control solutions that defeat the pathogen and preserve organ health are demonstrated for four different approaches for therapy. It is shown that control theory can point the way toward new protocols for treatment and remediation of human diseases.

Original languageEnglish (US)
Pages (from-to)91-104
Number of pages14
JournalOptimal Control Applications and Methods
Volume23
Issue number2
DOIs
StatePublished - Mar 1 2002

All Science Journal Classification (ASJC) codes

  • Control and Systems Engineering
  • Software
  • Control and Optimization
  • Applied Mathematics

Keywords

  • Bioinformatics
  • Biological modelling
  • Optimal control
  • Optimization

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    Stengel, R. F., Ghigliazza, R., Kulkarni, N., & Laplace, O. (2002). Optimal control of innate immune response. Optimal Control Applications and Methods, 23(2), 91-104. https://doi.org/10.1002/oca.704