Almost everyone is aware of the almost irresistible desire to sleep that occurs at the onset of “the flu.” Indeed, most loving parents or grandparents recommend sleep as a preventive measure and as an aid for recuperation from infection. Hippocrates dispensed similar advice; nevertheless, the investigation of relation­ ships between sleep and host defense systems had to wait 2100 years before being addressed scientifically. Within the past 10 years sleep responses to microbial challenge have been characterized as one component of the acute-phase response. These microbial-induced sleep responses may, in fact, contribute to host defense though this issue has yet to be satisfactorily resolved. Conversely, sleep loss is associated with changes in a variety of immune parameters and prolonged sleep loss with septicemia. The excess sleep associated with infectious challenge results from the amplification of physiological sleep mechanisms. Physiological sleep mechanisms include molecules that have traditionally been thought of as immune response modifiers but are now known to be constituitively expressed in brain and involved in several physiological regulations including sleep. This review will focus on some of the data that form the basis for these statements; it ends with a


short discussion of the theoretical implications these data have on sleep, function and brain organization as it applies to sleep.