Acute systemic inflammation transiently synchronizes clock gene expression in equine peripheral blood.

The research article discusses an experiment conducted on horses to determine whether acute systemic inflammation can synchronize the expression of clock genes, which are critical in maintaining innate immune responses and homeostasis, in equine blood.

Objective and Method

• The study sought to confirm if peripheral immune activation like acute systemic inflammation, could act as a resetting signal for the circadian clocks in non-oscillating tissues like equine peripheral blood by increasing clock gene expressions.
• The researchers observed the effect of in vivo administration of lipopolysaccharide (LPS), a molecule known to stimulate strong immune responses, on the upregulation of two core clock genes, Per2 and Bmal1.

Findings

• The researchers found that the administration of lipopolysaccharide resulted in a significant upregulation of the core clock genes Per2 and Bmal1 in equine blood.
• This upregulation was associated with an acute rise in tumor necrosis factor (TNF) alpha and core body temperature as compared to vehicles treated control horses.

Co-administration of LPS and Phenylbutazone

• A non-steroidal anti-inflammatory drug (NSAID), phenylbutazone was used alongside LPS to test its impact on the acute response. Phenylbutazone is known to inhibit prostaglandin (PG) E(2) synthesis in horses.
• The researchers found that this co-administration prevented the febrile response (rise in body temperature associated with illness) and the synchronized increase in clock gene expression seen in previous instances.

Ex Vivo Experiment

• Additional tests were conducted ex vivo using equine peripheral blood mononuclear cells (PBMCs) to determine if a heat shock mimicking in vivo fever or PGE(2) or LPS could replicate the rise in clock genes.
• This experiment did not result in an increase in the expression of Per2 and Bmal1, suggesting an indirect communication pathway between immune modulators and the molecular machinery of cell clocks in peripheral blood.

Implications of Findings

• The study may indicate a feedback mechanism that allows the immune system to play a role in regulating peripheral clocks- the circadian system that contributes to the innate immune responses and maintaining homeostasis.
• This suggests that the tissue acting as the first line of defense during infectious challenges, like peripheral blood, may have their circadian rhythms subtly adjusted by inflammation to better respond to the physiological changes induced by it.