Plenary
Lecture
Endotoxin Tolerance: Mathematical Models
Professor Mircea Olteanu
Mathematics Department
University Politehnica Bucharest, Romania
Email:
mirolteanu@yahoo.co.uk
Coauthos: Paul Flondor, Radu Dobrescu, Catalin
Vasilescu
Abstract:
Endotoxin tolerance is an important phenomenon of innate
immunity. It is usually defined as “a reduced
responsiveness to a lipopolysaccharide (LPS) challenge
following a first encounter with endotoxin.” The actors
of the endotoxin tolerance are a Gramnegative bacterial
lipopolysaccharide (LPS), the proinflammatory cytokines
(the best marker of the inflammatory process is
considered to be the TNFá) and the downregulating
factors. It has to be noted that there are three
possible outcomes at a secondary challenge with
endotoxin: 1) the first and the second responses have
the same magnitude, 2) the second response is greater
than the first one and 3) the second response is lower
than the first one. This last outcome is known as the
typical endotoxin tolerance phenomenon. There are many
reasons which explain the interest in understanding the
endotoxin tolerance (for example, the connections with
sepsis). It would be of great help to have a simple but
good enough mathematical model for testing and
simulating endotoxin tolerance in various reported
situations and also for a better understanding of the
factors acting during this complex phenomenon. In some
previous works the authors introduced an original
mathematical (ODE) model of endotoxin tolerance. The aim
of this lecture is to present this model and some new
improvements together with applications (mainly in
sepsis). Our original mathematical model of the
endotoxin tolerance is based on a generalized version of
the Michaelis  Menten  Hill equations for enzymatic
reactions. This is a nonlinear and non autonomous ODE 
time delayed system with LPS as an input. We also tried
to keep our model as simple as possible; the model could
be, of course, developed to a more sophisticated one. In
order to test our model we considered several typical
scenarios for the input (LPS challenge) such as: in
vivo, in vitro, immune paralysis (clinical sepsis). In
each case, the mathematical simulation fit wellenough
with the reported experimental data.
Brief Biografy of the Speaker:
Mircea Olteanu is professor at the Dept. of Mathematics
of the Politehnica University of Bucharest, Romania. His
area of study includes group representation theory, time
invariant systems, nonlinear analisys of time series and
mathematical modeling. He is the author of more than 40
scientific papers. Regarding the mathematical modeling
of the endotoxin tolerance (the subject of this plenary
lecture) he published several studies (as coauthor with
Paul Flondor, Catalin Vasilescu, Radu Dobrescu) in Amer.
J. of Surgery, Inflammation Research, Journal of
Critical Care, Chirurgia.
