炎症是免疫系统对有害刺激作出反应的关键机制之一。在炎症过程中，促炎与抗炎细胞因子相互作用以协调精细调控的动态免疫反应。这种细胞因子的相互作用决定了炎症反应的转换以及炎症反应的传播和发展。这种细胞因子相互作用的分子途径非常复杂，所以有必要进行时序监测，以便详细研究介质和细胞因子的作用。数学模型能够分析这个相互作用系统及其动态相互作用，从而推动我们对其的理解。因此，我们采用了数学建模方法，以肿瘤坏死因子(TNF)和白细胞介素10 (IL-10)为重点，研究了主要的促炎和抗炎细胞因子在脂多糖(LPS)刺激的原代人单核细胞中的相互作用。我们通过在不同时间点实验性地添加或阻断IL-10来生成相关的时序数据。该模型经过成功训练，能够预测独立验证数据，并可用于模拟解析在急性炎症事件中IL-10反馈的作用。我们利用这些见解得到了一个包含必要的IL-10介导反馈的简化预测模型。最后，经验证的简化模型被用于预测炎症反应中早期IL-10和TNF的转换。总的来说，我们对人单核细胞中炎症反应的精细调节获得了详细的洞察力，并提出了一个可以在研究细胞因子调控急性炎症复杂动态过程中进一步使用的模型。Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Inflammation is one of the vital mechanisms through which the immune system responds to harmful stimuli. During inflammation, pro and anti-inflammatory cytokines interplay to orchestrate fine-tuned, dynamic immune responses. The cytokine interplay governs switches in the inflammatory response and dictates the propagation and development of the inflammatory response. Molecular pathways underlying the interplay are complex, and time-resolved monitoring of mediators and cytokines is necessary as a basis to study them in detail. Our understanding can be advanced by mathematical models which enable to analyze the system of interactions and their dynamical interplay in detail. We, therefore, used a mathematical modeling approach to study the interplay between prominent pro and anti-inflammatory cytokines with a focus on tumor necrosis factor (TNF) and interleukin 10 (IL-10) in lipopolysaccharide (LPS)-primed primary human monocytes. Relevant time-resolved data were generated by experimentally adding or blocking IL-10 at different time points. The model was successfully trained and could predict independent validation data and was further used to perform simulations to disentangle the role of IL-10 feedbacks during an acute inflammatory event. We used the insight to obtain a reduced predictive model including only the necessary IL-10-mediated feedbacks. Finally, the validated reduced model was used to predict early IL-10 - TNF switches in the inflammatory response. Overall, we gained detailed insights into fine-tuning of inflammatory responses in human monocytes and present a model for further use in studying the complex and dynamic process of cytokine-regulated acute inflammation.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.