Dysregulation of Inflammatory Responses by Chronic Circadian Disruption

• DOI: 10.4049/jimmunol.1001026
• Publication Date: 2010-10-14T07:22:44Z
• Authors: Oscar Castanon-Ce...; Mingwei Wu; J Christopher Ehlen; Ketema Paul; Karen L Gamble; Russell L Johnson; Rachel C Besing; Michael Menaker; Andrew T Gewirtz; Alec J Davidson
• Keywords: Inflammation; Jet Lag Syndrome; 0301 basic medicine; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Polysomnography; Enzyme-Linked Immunosorbent Assay; Circadian Rhythm; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Biological Clocks; Macrophages, Peritoneal; Animals; Cytokines; Gene Knock-In Techniques

Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag animal models leads to a higher risk several pathologies. Many these conditions both workers and experimental share the common factor inflammation. In this study, we show that experimentally induced altered innate immune responses. Endotoxemic shock by LPS was magnified, leading hypothermia death after four consecutive weekly 6-h phase advances light/dark schedule, with 89% mortality compared 21% unshifted control mice. This may be due heightened release proinflammatory cytokines response treatment shifted animals. Isolated peritoneal macrophages harvested from mice exhibited similarly vitro, indicating cells are target for lag. Sleep deprivation stress known alter function potential mediators effects describe. However, polysomnographic recording exposed shifting schedule revealed no sleep loss, measures were not contrast, observed abolished expression clock genes central clock, liver, thymus, We conclude disruption, but loss stress, associated lag-related dysregulation system. Such changes might mechanism myriad negative health work.