Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation

Rami A. Namas, Qi Mi, Rajaie Namas, Khalid Almahmoud, Akram M. Zaaqoq, Othman Abdul-Malak, Nabil Azhar, Judy Day, Andrew Abboud, Ruben Zamora, Timothy R. Billiar, Yoram Vodovotz*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

64 Scopus citations

Abstract

Traumatic injury elicits a complex, dynamic, multidimensional inflammatory response that is intertwined with complications such as multiple organ dysfunction and nosocomial infection. The complex interplay between inflammation and physiology in critical illness remains a challenge for translational research, including the extrapolation to human disease from animal models. Recent Advances: Over the past decade, we and others have attempted to decipher the biocomplexity of inflammation in these settings of acute illness, using computational models to improve clinical translation. In silico modeling has been suggested as a computationally based framework for integrating data derived from basic biology experiments as well as preclinical and clinical studies. Critical Issues: Extensive studies in cells, mice, and human blunt trauma patients have led us to suggest (i) that while an adequate level of inflammation is required for healing post-trauma, inflammation can be harmful when it becomes self-sustaining via a damage-associated molecular pattern/Toll-like receptor-driven feed-forward circuit; (ii) that chemokines play a central regulatory role in driving either self-resolving or self-maintaining inflammation that drives the early activation of both classical innate and more recently recognized lymphoid pathways; and (iii) the presence of multiple thresholds and feedback loops, which could significantly affect the propagation of inflammation across multiple body compartments. Future Directions: These insights from data-driven models into the primary drivers and interconnected networks of inflammation have been used to generate mechanistic computational models. Together, these models may be used to gain basic insights as well as serving to help define novel biomarkers and therapeutic targets.

Original languageEnglish
Pages (from-to)1370-1387
Number of pages18
JournalAntioxidants and Redox Signaling
Volume23
Issue number17
DOIs
StatePublished - 10 Dec 2015
Externally publishedYes

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