Toxicity and neuroendocrine regulation of the immune response: a model analysis.

Various models have been proposed for the regulation of the primary immune response. Most of the models focus on the ability of the immune system to control a multiplying pathogen, and take into account the cross-regulations between different immune components. In the present study, we integrate the immune system in the general physiology of the host and consider the interaction between the immune and neuroendocrine systems. In addition to pathogen growth and toxicity, our four-variable model takes into account the toxic consequences for the organism of the immune response itself, as well as a neuro-hormonal retro-control of this immune response. Formally, the dynamics of the model is first explored on the basis of a discrete caricature, with special emphasis on the role of the constitutive feedback loops for determining the essential dynamical behavior of the system. This logical analysis is then completed by a classical continuous approach using differential equations. From a biological point of view, our model accounts for four stable regimes which can be described as "pathogen elimination/organism healthy", "pathogen elimination/ organism death", "pathogen growth/organism death" and "chronic infection". The size of the basins of attraction of these different regimes varies as a function of some crucial parameters. Our model allows moreover to interpret the interplay between pathogen immunogenicity and neuro-hormonal feedback, the effects of stress on immunity and the toxic shock syndrome, in terms of transitions among the steady states.