Neurobiological mechanisms of fever

Increased body temperature (fever or hyperthermia) is a physiological response to many different stimuli. In fact, fever (a 1-4 degrees C elevation of the body temperature) is not only a clinical symptom common to many infectious diseases but also a side effect of immunostimulating or antiviral therapies. Hyperthermic reactions, on the other hand, can be observed after treatment with antipsychotic drugs, 5-hydroxytryptamine-receptor agonists, and acetylcholinesterase inhibitors and as a reaction to anesthesia. Moreover, hyperthermic reactions can be related to particularly stressful emotional states, to the menstrual ovulatory cycle, and to pregnancy. Transient hyperthermia or fever is also a common consequence of cerebral ischemic events, and it is present during stress as well as intense physical exercise. This review focuses on fever, one of the main components of the systemic acute-phase reaction to external proinflammatory stimuli. Special emphasis is given to neuronal mechanisms of fever induction, in which the hypothalamus plays a crucial role in both control of the febrile response as well as other centrally mediated neurological signs of inflammation, such as increased sleep, activation of the hypothalamic-pituitary-adrenal axis, anorexia, and sickness behavior. This review pays particular attention to the role of proinflammatory cytokines as endogenous pyrogens.