Details

Autor(en) / Beteiligte

• Azhar, Nabil
• Namas, Rami A
• Almahmoud, Khalid
• Zaaqoq, Akram
• Malak, Othman A
• Barclay, Derek
• Yin, Jinling
• El-Dehaibi, Fayten
• Abboud, Andrew
• Simmons, Richard L
• Zamora, Ruben
• Billiar, Timothy R
• Vodovotz, Yoram

Titel

A putative "chemokine switch" that regulates systemic acute inflammation in humans

Ist Teil von

• Scientific reports, 2021-05, Vol.11 (1), p.9703-9703, Article 9703

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Systemic inflammation is complex and likely drives clinical outcomes in critical illness such as that which ensues following severe injury. We obtained time course data on multiple inflammatory mediators in the blood of blunt trauma patients. Using dynamic network analyses, we inferred a novel control architecture for systemic inflammation: a three-way switch comprising the chemokines MCP-1/CCL2, MIG/CXCL9, and IP-10/CXCL10. To test this hypothesis, we created a logical model comprising this putative architecture. This model predicted key qualitative features of systemic inflammation in patient sub-groups, as well as the different patterns of hospital discharge of moderately vs. severely injured patients. Thus, a rational transition from data to data-driven models to mechanistic models suggests a novel, chemokine-based mechanism for control of acute inflammation in humans and points to the potential utility of this workflow in defining novel features in other complex diseases.