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Disorder of Systemic Inflammation in Sepsis and Trauma: A Systems Perspective

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Complex Systems and Computational Biology Approaches to Acute Inflammation

Abstract

The inflammatory response is highly integrated and involves regulatory elements released from the cells of the immune system, humoral factors, the endothelium, and endogenous danger signals. Once activated, the goals of the inflammatory response are to activate the cellular immune response in order to ward off penetrating pathogens and to initiate tissue repair mechanisms. The magnitude of the systemic response is proportional to the severity of the initial insult on the background of the genetic milieu of the individual. The inflammatory response is closely regulated, and a counter-anti-inflammatory response keeps it in check. When excessive or sustained, this immunoinflammatory response gives way to prolonged immunosuppression, leaving the individual susceptible to nosocomial infections and prolonged intensive care unit (ICU) stay. Only by understanding how the immunoinflammatory response becomes disordered can we devise strategies to limit the deleterious consequences.

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Abbreviations

APC:

Antigen-presenting cell

AR:

Adrenergic receptors

AT:

Antithrombin

BLyS:

B-lymphocyte stimulator

Breg:

Regulatory B cell

CLP:

Cecal ligation and puncture

CLR:

C-type lectin receptor

COX2:

Cyclooxygenase-2

CRH:

Corticotropin-releasing hormone

CTL:

Cytotoxic T cells

DAMP:

Damage-associated molecular pattern

DC:

Dendritic cell

DNA:

Deoxyribonucleic acid

GM-CSF:

Granulocyte-macrophage colony stimulating factor

GPCR:

G-protein-coupled receptors

HIF-1:

Hypoxia inducible factor-1

HMGB1:

High-mobility group box 1

ICAM1:

Intercellular adhesion molecule-1

ICU:

Intensive care unit

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MAC:

Membrane attack complex

MAPK:

Mitogen-activated protein kinase

MCP-1:

Macrophage chemoattractant protein-1

MDSC:

Myeloid-derived suppressor cell

MHC I:

Major histocompatibility class I

MHC II:

Major histocompatibility class II

MIG:

Monokine induced by gamma interferon

MIP-1α:

Macrophage inflammatory protein-1 alpha

MODS:

Multiple organ dysfunction syndrome

MyD88:

Myeloid differentiation primary response gene 88

NADPH:

Nicotinic adenine dinucleotide phosphate

NET:

Neutrophil extracellular trap

NF-κB:

Nuclear factor kappa B

NK:

Natural killer

NKT:

Natural killer T

NLR:

NOD-like receptors

NO:

Nitric oxide

PAMP:

Pathogen-associated molecular pattern

PGI2:

Prostaglandin I2

PGN:

Peptidoglycan

PHD-2:

Proline-hydroxylase-2

PMN:

Polymorphonuclear neutrophils

PRR:

Pattern-recognition receptor

RAGE:

Receptor for advanced glycation end products

RANTES:

Regulated on activation normal T cell expressed and secreted

RCT:

Randomized, placebo-controlled clinical trial

RLR:

RIG-I like receptors

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SIRS:

Systemic inflammatory response syndrome

SOFA:

Sequential organ failure assessment

TF:

Inflammation is tissue factor

TFPI:

Tissue factor pathway inhibitor

TGF-β1:

Transforming growth factor-β1

Th:

T helper cell

Th1:

T helper type 1

Th2:

T helper type 2

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

Treg:

Regulatory T cell

TRIF:

TIR-domain containing adaptor-inducing interferon-β

VACM1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

VHL:

von-Hippel-Lindau

VWF:

Von Willebrand factor

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Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Jillian W. Bonaroti, Kent R. Zettel, Timothy R. Billiar & Matthew D. Neal

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  2. Kent R. Zettel
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Correspondence to Timothy R. Billiar .

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  1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Yoram Vodovotz

  2. Department of Surgery, University of Vermont, Burlington, VT, USA

    Gary An

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Bonaroti, J.W., Zettel, K.R., Billiar, T.R., Neal, M.D. (2021). Disorder of Systemic Inflammation in Sepsis and Trauma: A Systems Perspective. In: Vodovotz, Y., An, G. (eds) Complex Systems and Computational Biology Approaches to Acute Inflammation. Springer, Cham. https://doi.org/10.1007/978-3-030-56510-7_6

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