Thermoregulation Part II

From Basic Neuroscience to Clinical Neurology

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• Publisher: Elsevier
• Year: 2018
• Print ISBN: 9780444640741
• eBook ISBN: 9780444640758
• Topic: Médecine
• Subtopic: Neurologie

Thermoregulation, Part II: From Basic Neuroscience to Clinical Neurology, Volume 155, not only reviews how body temperature regulation changes in neurological diseases, but also how this aspect affects the course and outcomes of each disease. Other sections of the volume review three therapeutic approaches that are aimed at manipulating body temperature, including induced hypothermia, induced hyperthermia and antipyretic therapy. The book is comprised of nine sections across two volumes, five dealing with the basic aspects of body temperature regulation and four dealing with the clinical aspects. Basic sections cover the Thermoregulation system, Thermoreceptors, Thermoeffectors, Neural pathways, and Thermoregulation as a homeostatic function. In addition, the book covers the physiology and neuroanatomy of the thermoregulation system and provides descriptions of how the regulation of body temperature intervenes with other physiological functions (such as sleep, osmoregulation, and immunity), stress, exercise and aging. Basic sections serve as an introduction to the four clinical sections: Body Temperature, Clinical Significance, Abnormal Body Temperature, Thermoregulation in Neurological Disease and Therapeutic Interventions. - Presents a clear, logical pathway from the fundamental physiology of thermoregulation, through neurobiology, to clinical applications and disease - Enables researchers and clinicians to better understand the value of temperature measurement in disease and the use of temperature as a therapy - Integrates content from a broad field of research, including topics on the molecular physiology of temperature receptors, to the management of accidental hypothermia

Chapter 34

Fever and hypothermia in systemic inflammation

Andras Garami^1,*; Alexandre A. Steiner²; Andrej A. Romanovsky^{3 1} Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
² Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
³ Thermoregulation and Systemic Inflammation Laboratory (FeverLab), Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States
^* Correspondence to: Andras Garami, M.D., Ph.D., Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti Str., Pécs, H7624, Hungary. Tel: + 36-72-536-246 email address: [email protected]

Abstract

Systemic inflammation-associated syndromes (e.g., sepsis and septic shock) often have high mortality and remain a challenge in emergency medicine. Systemic inflammation is usually accompanied by changes in body temperature: fever or hypothermia. In animal studies, systemic inflammation is often modeled by administering bacterial lipopolysaccharide, which triggers autonomic and behavioral thermoeffector responses and causes either fever or hypothermia, depending on the dose and ambient temperature. Fever and hypothermia are regulated changes of body temperature, which correspond to mild and severe forms of systemic inflammation, respectively. Mediators of fever and hypothermia are called endogenous pyrogens and cryogens; they are produced when the innate immune system recognizes an infectious pathogen. Upon an inflammatory challenge, hepatic and pulmonary macrophages (and later brain endothelial cells) start to release lipid mediators, of which prostaglandin (PG) E₂ plays the key role, and cytokines. Blood PGE₂ enters the brain and triggers fever. At later stages of fever, PGE₂ synthesized within the blood-brain barrier maintains fever. In both cases, PGE₂ is synthesized by cyclooxygenase-2 and microsomal PGE₂synthase-1. Mediators of hypothermia are not well established. Both fever and hypothermia are beneficial host defense responses. Based on evidence from studies in laboratory animals and clinical trials in humans, fever is beneficial for fighting mild infection. Based mainly on animal studies, hypothermia is beneficial in severe systemic inflammation and infection.

Keywords

body temperature; cyclooxygenase; endotoxin; LPS; neuropeptide; prostaglandin; sepsis; shock; sickness syndrome; SIRS; thermoregulation

Abbreviations

2-AG;2-arachidonoyl-glycerol; 2-arachidonoyl-glycerol; AA; arachidonic acid; arachidonic acid; AEA; N-arachydonoyl-ethanolamine; N-arachydonoyl-ethanolamine; BAT; brown adipose tissue; brown adipose tissue; BBB; blood-brain barrier; blood-brain barrier; CB; cannabinoid; cannabinoid; COX; cyclooxygenase; cyclooxygenase; DAG; diacylglycerol; diacylglycerol; DMH; dorsomedial hypothalamus; dorsomedial hypothalamus; EET; epoxyeicosatrienoic acid; epoxyeicosatrienoic acid; GABA; γ-aminobutyric acid; γ-aminobutyric acid; H-PGDS; hematopoietic PGD₂ synthase; hematopoietic PGD₂ synthase; i.c.v.; intracerebroventricular(ly); intracerebroventricular(ly); IL; interleukin; interleukin; i.p.; intraperitoneal(ly); intraperitoneal(ly); i.v.; intravenous(ly); intravenous(ly); LOX; lipoxygenase; lipoxygenase; LPS; lipopolysaccharide; lipopolysaccharide; LT; leukotriene; leukotriene; m; microsomal; microsomal; MAG; monoacylglcerol; monoacylglcerol; MnPO; median preoptic nucleus; median preoptic nucleus; MPO; medial preoptic area; medial preoptic area; NLR; nucleotide-binding oligomerization domain-like receptor; nucleotide-binding oligomerization domain-like receptor; PAF; platelet-activating factor; platelet-activating factor; PAMP; pathogen-associated molecular patterns; pathogen-associated molecular patterns; PG; prostaglandin (e.g., in PGE₂); prostaglandin (e.g., in PGE₂); PGDS; PGD₂ synthase; PGD₂ synthase; PGES; PGE₂ synthase; PGE₂ synthase; PL; phospholipase (e.g., in PLA₂); phospholipase (e.g., in PLA₂); POA; preoptic area; preoptic area; PRR; pattern recognition receptor; pattern recognition receptor; PVH; paraventricular hypothalamus; paraventricular hypothalamus; RANKL; receptor activator of NF-κB ligand; receptor activator of NF-κB ligand; SIRS; systemic inflammatory response syndrome; systemic inflammatory response syndrome; T_a, T_b, and T_sk; ambient, body, and skin temperatures; ambient, body, and skin temperatures; TLR; Toll-like receptor; Toll-like receptor; TNF-α; tumor necrosis factor-α; tumor necrosis factor-α; TRPV1; transient receptor potential vanilloid-1 (channel); transient receptor potential vanilloid-1 (channel); TXA₂; thromboxane A₂; thromboxane A₂; Vo₂; rate of oxygen consumption; rate of oxygen consumption

Introduction¹

Systemic inflammation is a generalized pathologic process, which can be clinically manifested in various forms, including systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple-organ dysfunction and failure (Bone et al., 1992). The inflammatory response is a series of complex pathophysiologic events that can result from infections, as well as from noninfectious causes, such as trauma or burns (Balk, 2014). When the underlying cause of the systemic inflammatory response is infection, it is termed sepsis.

The exact definitions and clinical criteria of sepsis and related syndromes have changed over the past three decades (Bone et al., 1992; Levy et al., 2003; Singer et al., 2016). According to the latest consensus (Singer et al., 2016), sepsis is defined as evidence of infection plus life-threatening organ dysfunction. Even nowadays, it constitutes a global burden for healthcare, with an estimated 31 million cases and 5.3 million deaths worldwide annually (Fleischmann et al., 2016) and an incidence rate of ~ 30% in patients admitted to the intensive care unit (Vincent et al., 2014). Of note, not only can sepsis lead to death acutely, but it also increases the risk of death for 5–8 years after the septic event (Quartin et al., 1997; Dreiher et al., 2012). In the United States, the incidence of hospitalizations with sepsis increased by ~ 50% between 2003 and 2009 (Walkey et al., 2015), with estimated annual healthcare costs exceeding $17 billion nationally (Angus et al., 2001).

The importance of a change (elevation) in body temperature (T_b) in inflammation was recognized a long time ago. This is also reflected in the word inflammation, as it originates from the Latin inflammare (to set on fire). Fever was recognized as a disease symptom already in the time of Hippocrates (5th–4th century bc) (Atkins, 1982). Heat (calor) is also one of the four cardinal symptoms of inflammation, along with redness, swelling,...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Handbook of Clinical Neurology 3rd Series
• Foreword
• Preface
• Contributors
• Chapter 29: Body temperature and clinical thermometry
• Chapter 30: Brain temperature: from physiology and pharmacology to neuropathology
• Chapter 31: Heat exhaustion
• Chapter 32: Heatstroke
• Chapter 33: Accidental hypothermia
• Chapter 34: Fever and hypothermia in systemic inflammation
• Chapter 35: Stress-induced hyperthermia and hypothermia
• Chapter 36: Body temperature regulation and drugs of abuse
• Chapter 37: Body temperature regulation and anesthesia
• Chapter 38: Malignant hyperthermia
• Chapter 39: Neuroleptic malignant syndrome and serotonin syndrome
• Chapter 40: Acral coldness – severely reduced blood flow to fingers and toes
• Chapter 41: Consequences of perioperative hypothermia
• Chapter 42: Thermoregulatory dysfunction in multiple sclerosis
• Chapter 43: Thermoregulation in Parkinson disease
• Chapter 44: Hypothermia as a risk factor for Alzheimer disease
• Chapter 45: Thermoregulation in epilepsy
• Chapter 46: Thermoregulation in amyotrophic lateral sclerosis
• Chapter 47: Thermoregulatory disorders in Huntington disease
• Chapter 48: Thermoregulation in neuropathies
• Chapter 49: Thermoregulation in brain injury
• Chapter 50: Thermoregulation following spinal cord injury
• Chapter 51: Hypothermia in acute ischemic stroke therapy
• Chapter 52: Selective brain hypothermia
• Chapter 53: Therapeutic hyperthermia
• Chapter 54: Antipyretic therapy: clinical pharmacology
• Index