UC Berkeley

The effect of circadian rhythm (CR) disruption on immune function depends on the method by which CRs are disrupted. Behavioral and thermoregulatory responses induced by lipopolysaccharide (LPS) treatment were assessed in female Siberian hamsters in which circadian locomotor activity (LMA) rhythms were eliminated by exposure to a disruptive phase-shifting protocol (DPS) that sustains arrhythmicity even when hamsters are housed in a light-dark cycle. This noninvasive treatment avoids genome manipulations and neurological damage associated with other models of CR disruption. Circadian rhythmic (RHYTH) and arrhythmic (ARR) hamsters housed in a 16L:8D photocycle were injected with bacterial LPS near the onset of the light (zeitgeber time 1; ZT1) or dark (ZT16) phase. LPS injections at ZT16 and ZT1 elicited febrile responses in both RHYTH and ARR hamsters, but the effect was attenuated in the arrhythmic females. In ZT16, LPS inhibited LMA in the dark phase immediately after injection but not on subsequent nights in both chronotypes; in contrast, LPS at ZT1 elicited more enduring (~4 day) locomotor hypoactivity in ARR than in RHYTH hamsters. Power and period of dark-phase ultradian rhythms (URs) in LMA and Tb were markedly altered by LPS treatment, as was the power in the circadian waveform. Disrupted circadian rhythms in this model system attenuated responses to LPS in a trait- and ZT-specific manner; changes in UR period and power are novel components of the acute-phase response to infection that may affect energy conservation.