Sleep and Host Defense

CHAPTER HIGHLIGHTS

• That sleep is altered during sickness has been known for millennia. Yet, systematic and controlled studies aimed at elucidating the extent to which sleep is altered in response to immune challenge have only been conducted during the last 30 years.

• Substances historically viewed as components of the innate immune system are now known to be involved in the regulation or modulation of physiological sleep-wake behavior, in the absence of immune challenge. Changes in sleep during immune challenge are actively driven and result from amplification of these physiological mechanisms.
   
• Although the precise changes in sleep-wake behavior depend on the pathogen, route of infection, timing of infection, host species, and other factors, altered sleep during immune challenge is generally characterized by periods of increased non-rapid eye movements (NREM) sleep, increased delta power during NREM sleep, and suppressed REM sleep. Infection-induced alterations in sleep are often accompanied by fever or hypothermia.
   
• Altered sleep has been studied in humans during pathologies and/or infections with pathogens including HIV/AIDS, rhinovirus (common cold), streptococci, trypanosomes, prions, and sepsis. Laboratory animal models include sepsis, influenza and other viruses (gammaherpes virus, vesicular stomatitis virus, rabies, feline immunodeficiency virus), several bacterial species, trypanosomes, and several prion diseases.
   
• Mechanisms that link sleep to innate immunity involve a biochemical brain network composed of cytokines, chemokines, growth factors, transcription factors, neurotransmitters, enzymes and their receptors.  Each of these substances and receptors is present in neurons, although interactions with glia are critical for host defense responses to immune challenge. Redundancy, feed-forward, and feed-back loops are characteristic of this biochemical network. These attributes provide stability and flexibility to the organismal response to immune challenge.