Interleukin‐17 as a spatiotemporal bridge from acute to chronic inflammation: Novel insights from computational modeling

Abstract

A systematic review of several acute inflammatory diseases ranging from sepsis and trauma/hemorrhagic shock to the relevant pathology of the decade, COVID‐19, points to the cytokine interleukin (IL)‐17A as being centrally involved in the propagation of inflammation. We summarize the role of IL‐17A in acute inflammation, leveraging insights made possible by biological network analysis and novel computational methodologies aimed at defining the spatiotemporal spread of inflammation in both experimental animal models and humans. These studies implicate IL‐17A in the cross‐tissue spread of inflammation, a process that appears to be in part regulated through neural mechanisms. Although acute inflammatory diseases are currently considered distinct from chronic inflammatory pathologies, we suggest that chronic inflammation may represent repeated, cyclical episodes of acute inflammation driven by mechanisms involving IL‐17A. Thus, insights from computational modeling of acute inflammatory diseases may improve diagnosis and treatment of chronic inflammation; in turn, therapeutics developed for chronic/autoimmune disease may be of benefit in acute inflammation. This article is categorized under: Immune System Diseases > Computational Models

Add fuel to the fire: Inflammation and immune response in lung cancer combined with COVID-19

“…Among them, inflammation is an important link; it has a bifacial nature and can not only promote immune responses but also lead to immunosuppression. Some scholars have suggested ( 114 ) that although the pathological manifestations of acute inflammation and chronic inflammation are different, the driving mechanism of the two is relevant. As such, starting with acute inflammatory diseases may improve the diagnosis and treatment of chronic inflammation; conversely, therapies developed for chronic diseases may be beneficial for acute inflammation.…”

What’s next for computational systems biology?

“…Of course, once reliable whole-cell models are feasible, the next targets will be models of tissues, organs, and even entire organisms, which will be discussed later in greater detail. Indeed, there is much excitement about "digital twins," which are envisioned as computational analogs of individuals that will be so realistic that reliable experiments can be done computationally before the real-world individual is treated for a disease (Li et al, 2008;Shah et al, 2023). This aspect of the future is already underway, and various computational platforms have been proposed, including the Virtual Liver (Virtual_Liver, 2011), Virtual Brain (Virtual_Brain, 2023), Virtual Rat (University of Michigan, 2019), and ELIXIR (Martins dos Santos et al, 2022).…”

“…Modeling macroscopic outcomes alone may oversimplify the state of the body, whereas modeling the cellular and molecular underpinnings of disease alone may lead to findings that are often irrelevant at the clinical scale. The need to augment in vitro data with in vivo data from both healthy and diseased animals and patient models across all systems biological projects will be critical as we trend toward developing digital twin models of pathologic states (Shah et al, 2023;Vodovotz, 2023). Traditional statistics will provide the core tools for rigorously testing the validity of experimentally inferred differences across time, patients, and datasets.…”

The applications of functional materials-based nano-formulations in the prevention, diagnosis and treatment of chronic inflammation-related diseases

“…The main categories are acute inflammation and chronic inflammation. Acute inflammation is defined as inflammation that occurs in the short term through interactions between innate immune cells and pathogens or in response to harmful stimuli during cellular stress or injury, while chronic inflammation usually persists through the latter and eventually damages tissues and organs to cause chronic inflammatory disease ( Furman et al, 2019 ; Reichardt et al, 2021 ; Shah et al, 2023 ). The inflammatory response process can be divided into 1) damage to the body’s tissues and cells, 2) recognition of damage factors and tissue necrosis and production of inflammatory mediators, 3) dilution, neutralization, killing and removal of harmful substances, 4) abatement and termination of the inflammatory response, and 5) repair of damaged tissues ( Chen et al, 2018 ; Schett and Neurath, 2018 ; Reichardt et al, 2021 ).…”