Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels

Golden-mantled ground squirrels (Spermophilus lateralis) undergo seasonal hibernation during which core body temperature (Tb) values are maintained 1-2°C above ambient temperature. Hibernation is not continuous. Squirrels arouse at ∼7-day intervals, during which Tb increases to 37°C for ∼16 h; thereafter, they return to hibernation and sustain low TbS until the next arousal. Over the course of the hibernation season, arousals consume 60-80% of a squirrel\u27s winter energy budget, but their functional significance is unknown and disputed. Host-defense mechanisms appear to be down regulated during the hibernation season and preclude normal immune responses. These experiments assessed immune function during hibernation and subsequent periodic arousals. The acute-phase response to bacterial lipopolysaccharide (LPS) was arrested during hibernation and fully restored on arousal to normothermia. LPS injection (ip) resulted in a 1-1.5°C fever in normothermic animals that was sustained for \u3e8 h. LPS was without effect in hibernating squirrels, neither inducing fever nor provoking arousal, but a fever did develop several days later, when squirrels next aroused from hibernation; the duration of this arousal was increased six fold above baseline values. Intracerebroventricuiar infusions of prostaglandin E2 provoked arousal from hibernation and induced fever, suggesting that neural signaling pathways that mediate febrile responses are functional during hibernation. Periodic arousals may activate a dormant immune system, which can then combat pathogens that may have been introduced immediately before or during hibernation