Fever and hypothermia in systemic inflammation

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