Dynamical modeling of pro- and anti-inflammatory cytokines in the early stage of septic shock

Abstract

A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.

Resolvin D5 (RvD5) Reduces Renal Damage Caused by LPS Endotoxemia in Female Mice

“…Thus, the resultant inflammation depends on the balance between pro-and anti-inflammatory cytokines. Some drugs may act by increasing IL-10 levels beyond regular production, which results in a reduction of inflammation [22][23][24]. RvD5 did not alter IL-10 production in the kidneys caused by LPS endotoxemia (Figure 3D), which suggests that this lipid was not acting by, for instance, up-regulating IL-10 production.…”

“…We started by performing a dose-response curve to evaluate the activity of RvD5 (0.1; 1 or 10 ng/animal, i.p.). We used a pharmacological approach to test RvD5 as a drug; however, the selected dose range was based on literature data that was obtained using up to 10 ng of RvD5 with positive activities [19], as well as data on cellular and tissue production of RvD5, detecting levels ranging from approximately 100 pg and 10 ng [22][23][24]. Blood levels of urea and creatinine, which are clinical markers of kidney injury, were measured 6 h after LPS stimulation in plasma samples.…”

A dynamic inflammation model for neutrophil and monocyte responses in sepsis, trauma and surgery patient clusters

“…IL6 and IL10 signal to cells by attaching to their surface via specific receptors. Tallon et al 17 used IL10 to represent the anti-inflammatory signal in their model of pro- and anti-inflammatory cytokines in the early stages of septic shock.…”

“…Sepsis advances rapidly and the immune system is strongly involved, with 60% of the patient's genome altered within 30 minutes of hospital admission 15 and cytokines and receptors linked to increased inflammation and innate immune response particularly affected 15 . IL6 and IL10 are pro-and antiinflammatory cytokines, that have been used as inflammation markers in several models [16][17][18][19] and shown to increase production rates of altered neutrophils and monocytes in-vitro…”

“…Having defined the clusters, we represent them with a dynamical model based on chemical engineering principals The model is shown in Figure1. It represents the evolution of neutrophils, monocytes and HLA-DR proteins through the bone marrow and into the circulation under the influence of an inflammation function, ‫ܨ‬17 . The model is comprised of mass balances and represents the bone marrow and blood circulation as a series of stirred tanks or compartments.…”