Our project builds on iterative interaction between modeling (data-driven and mechanistic [differential equation-based]) and experiments to determine how brainstem inflammation limits variability of physiologic patterns and uncouples biologic rhythms. Specifically, we ask do increases in the predictability of ventilatory pattern variability (VPV) and/or decreases in cardio-respiratory coupling (CRC) reflect increases in proinflammatory cytokines in the ponto-medullary circuitry controlling homeostasis. Our primary goal is to determine if quantifying VPV and CVC produce biometrics that track a health and herald the onset of sepsis. The biologic domains of the model are the expression and control of the inflammatory cytokines in the nucleus tractus solitarii, nucleus Ambiguus, and Kölliker-Fuse nuclei, which are critical nuclei in brainstem control circuits of the cardiac, sympathetic and respiratory effectors. Thus, in the experimental protocol the time scales correspond to:  1) the 10-100 milliseconds involved in the time course of cytokines effecting the synaptic efficacy in the control circuits, 2) the 0.1-1 or 1-5 seconds involved in the expression of the cardiac and respiratory cycles in rats and humans, respectively, 3) 6 - 48 hours involved in tracking the development of sepsis after systemic inoculation in rats and 4) 1-7 days in tracking critically ill patients. Currently, in the mechanistic model, we are focusing on the interaction between the autonomic and respiratory effectors, i.e., drawing scalable models for investigating the neural control of respiratory-modulation of heart rate and blood pressure and the tendency for respiratory rhythm to be delayed with increases in arterial pulse pressure. In the data-driven models of central cytokine expression, the time scales are 6-48 hours.