Tracking inflammation status for improving patient prognosis: A review of current methods, unmet clinical needs and opportunities

Abstract

Inflammation is the body's response to infection, trauma or injury and is activated in a coordinated fashion to ensure the restoration of tissue homeostasis and healthy physiology. This process requires communication between stromal cells resident to the tissue compartment and infiltrating immune cells which is dysregulated in disease. Clinical innovations in patient diagnosis and stratification include measures of inflammatory activation that support the assessment of patient prognosis and response to therapy. We propose that (i) the recent advances in fast, dynamic monitoring of inflammatory markers (e.g., cytokines) and (ii) data-dependent theoretical and computational modeling of inflammatory marker dynamics will enable the quantification of the inflammatory response, identification of optimal, disease-specific biomarkers and the design of personalized interventions to improve patient outcomes - multidisciplinary efforts in which biomedical engineers may potentially contribute. To illustrate these ideas, we describe the actions of cytokines, acute phase proteins and hormones in the inflammatory response and discuss their role in local wounds, COVID-19, cancer, autoimmune diseases, neurodegenerative diseases and aging, with a central focus on cardiac surgery. We also discuss the challenges and opportunities involved in tracking and modulating inflammation in clinical settings.

Keywords: Acute phase proteins; Cytokines; Data-driven modeling; Health prognostics; Hormones; Inflammatory biomarkers; Wearable health monitoring.

Fig. 1.

Overview of the inflammatory response. Immune threats (injury, surgery, bacterial or viral infections, cancer, autoimmune diseases etc.) stimulate the secretion of cytokines from various host cells. Beyond the control of local inflammation, cytokines control various physiological processes, including activation of the HPA axis to produce ACTH and cortisol. Cortisol dampens cytokine activities through its anti-inflammatory action on cytokine production, and the inflammatory response is a result of the combined cytokine-HPA axis actions, which sequence the required repair and restorative mechanisms in the body.

Fig. 2.

Conceptual depiction of cytokine signaling mechanisms (autocrine, juxtacrine, paracrine and transsignaling) and examples of cytokines exhibiting them. Created with BioRender.com.

Fig. 3.

Proposed pipeline for longitudinal inflammatory marker data collection using novel wearable, portable and point of care testing devices Kurabayashi and Park (2023); Upton et al. (2023); Tu et al. (2023) and computational modeling and analysis e.g., Raju et al. (2023a, for providing insights on the biological and clinical aspects of systemic inflammation.

Fig. 4.

System-level description of inflammatory response to cardiac surgery. The signaling effects between the inflammatory markers and the effect of medication need to be mathematically quantified in a patient-specific manner through mechanistic modeling. Created with BioRender.com.

Fig. 5.

Overview of the inflammatory response to cardiac surgery with a focus on the role of most commonly studied cytokines and their observed relation to patient outcomes, and the systemic inflammation response involving hormone and acute phase protein secretion McGuinness et al. (2008); McBride et al. (1995); Tønnesen et al. (1996); Galvis et al. (2022); Mahle et al. (2014).