Protracted increases in core body temperature and interleukin-1 following acute administration of lipopolysaccharide: Implications for the stress response

Administration of lipopolysaccharide (LPS) produces a fever response often precipitated by the production of pro-inflammatory cytokines in the CNS. This pro-inflammatory cascade has traditionally been regarded as a transitory event that, with a non-replicating antigen such as LPS, would subside within a few hours. We present data showing that central and peripheral levels of IL-1 were substantially elevated as much as 48 h after LPS in some structures. In order to explore other aspects of the sickness response that might follow a similarly protracted time course, rats were implanted with telemetry probes and injected (i.p.) with 0, 10 or 100 μg/kg of LPS and left undisturbed for 96 h. Rats injected with LPS evinced a polyphasic fever with intermediate temperature peaks at approximately 5 and 8 h. Although the fever appeared to subside during the first night cycle, more detailed analysis confirmed that it was masked by the circadian rise in core temperature during the dark cycle and actually persisted for approximately 36 h following LPS. In contrast, LPS produced a transient suppression of social interaction that was no longer evident 24 h after LPS. Finally, we report that prior LPS produced a sensitized fever response to social conflict 48 h later. Taken together, these results suggest that acute administration of LPS results in a protracted fever response and increased IL-1 that persist for at least 24-48 h, and that LPS may render certain aspects of the stress response to a sensitized state.