Disease is an ever-present threat to the survival of the individual. To meet these challenges, higher organisms have developed complex mechanisms designed to heal and fight for survival. These mechanisms manifest as physiologic and behavioral alterations including fever, anorexia, malaise and loss of body weight (collectively the sickness response). Previous research has demonstrated that these effects are mediated by cytokine signaling. Our lab has contributed to this body of knowledge by showing that inflammatory cytokines directly modulate the activity of the central melanocortin and orexin signaling systems. However, much remains unknown about the role of central nervous system inflammation and how cytokine signaling is transmitted from the periphery to the central nervous system.
The data presented in this thesis contribute to the understanding of how cytokines act to stimulate physiologic and behavioral modifications that promote survival and healing. The novel implication that fenestrated capillary-specific signaling mechanisms are responsible for these behaviors represents a new potential for therapeutic interventions.