TOXICITY AND NEUROENDOCRINE REGULATION OF THE IMMUNE-RESPONSE - A MODEL ANALYSIS

Various models have been proposed for the regulation of the primary im mune response. Most of these models focus on the ability of the immune system to control a multiplying pathogen, and take into account the c ross-regulations between different immune components. In the present s tudy, we integrate the immune system in the general physiology of the host and consider the interaction between the immune and neuroendocrin e systems. In addition to pathogen growth and toxicity, our four-varia ble model takes into account the toxic consequences for the organism o f the immune response itself, as well as a neuro-hormonal retro-contro l of this immune response. Formally, the dynamics of the model is firs t explored on the basis of a discrete caricature, with special emphasi s on the role of the constitutive feedback loops for determining the e ssential dynamical behavior of the system. This logical analysis is th en completed by a classical continuous approach using differential equ ations. From a biological point of view, our model accounts for four s table regimes which can be described as ''pathogen elimination/organis m healthy'', ''pathogen elimination/organism death'', ''pathogen growt h/organism death'' and ''chronic infection''. The size of the basins o f attraction of these different regimes varies as a function of some c rucial parameters. Our model allows moreover to interpret the interpla y between pathogen immunogenicity and neuro-hormonal feedback, the eff ects of stress on immunity and the toxic shock syndrome, in terms of t ransitions among the steady states. (C) 1996 Academic Press Limited