RESUMO
The suprachiasmatic nucleus (SCN) drives circadian rhythms in behavioral and physiological variables, including the inflammatory response. Shift work is known to disturb circadian rhythms and is associated with increased susceptibility to develop disease. In rodents, circadian disruption due to shifted light schedules (jet lag) induced increased innate immune responses. To gain more insight into the influence of circadian disruption on the immune response, we characterized the inflammatory response in a model of rodent shift work and demonstrated that circadian disruption affected the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. Since food consumption is a main disturbing element in the shift work schedule, we also evaluated the inflammatory response to LPS in a group of rats that had no access to food during their working hours. Our results demonstrated that the shift work schedule decreased basal TNF-α levels in the liver but not in the circulation. Despite this, we observed that shift work induced increased cytokine response after LPS stimulation in comparison to control rats. Also, Kupffer cells (liver macrophages) isolated from shift work rats produced more TNF-α in response to in vitro LPS stimulation, suggesting important effects of circadian desynchronization on the functionality of this cell type. Importantly, the effects of shift work on the inflammatory response to LPS were prevented when food was not available during the working schedule. Together, these results show that dissociating behavior and food intake from the synchronizing drive of the SCN severely disturbs the immune response.
Assuntos
Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano , Ingestão de Alimentos , Inflamação/etiologia , Lipopolissacarídeos/imunologia , Animais , Relógios Biológicos/fisiologia , Células Cultivadas , Transtornos Cronobiológicos/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Células de Kupffer/imunologia , Células de Kupffer/metabolismo , Lipopolissacarídeos/administração & dosagem , Fígado/imunologia , Fígado/metabolismo , Masculino , Fotoperíodo , Ratos Wistar , Núcleo Supraquiasmático/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Tolerância ao Trabalho ProgramadoRESUMO
Several studies have shown circadian variations in the response of the immune system suggesting a role of the suprachiasmatic nucleus (SCN). Here we show that lipopolysaccharide (LPS) administration in the beginning of the active period induced more severe responses in temperature and cytokines than LPS given in the rest period. Moreover night administered LPS increased SCN basal neuronal activity indicating a direct influence of inflammation on the SCN. Bilateral lesions of the SCN resulted in an increased inflammatory response to LPS demonstrating that an interaction between the SCN and the immune system modulates the intensity of the inflammatory response.