A Rose by any Other Name: Towards a quantitative theory of neuroimmune interactions

Abstract Humanity has known about – and been fascinated by – the connection between mind and body since time immemorial, yet we have only been able to quantitatively explore their interactions in recent years. Even so, this field of neuroimmunology, broadly conceived, is categorically in its infancy. Despite myriad and diverse experimental reports, no coherent theoretical approach to the neuroimmune system has been even attempted, which makes it difficult to make sense of the emerging body of empirical findings. Here, we take the first steps towards this goal by introducing a mathematical framework that describes the triggering and control of neurological memories of immune challenges, also known as engrams. Using peanut allergies as a model system, we show how a simple differential equation model of coupled ‘immune-engram’ responses can explain a number of key observations regarding putative neurological control of focal inflammatory responses and failures thereof. Simulations of our model identify four areas of the parameter regime corresponding to distinct consequences of ‘fake’ immune stimulation: a) resolution b) finite oscillations of inflammation, followed by resolution c) sustained, self-amplifying oscillations (cytokine storm-like phenomena) and d) resolution followed by the permanent establishment of a chronic higher-baseline inflammatory state. We conclude with remarks around clinical implications as well as directions for future work in theoretical neuroimmunology.