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Time of day influences cytokine and clock gene response to immune stimulation in equine whole blood
Author(s) -
McGlynn O. F.,
Browne J. A.,
Blake C. M.,
Murphy B. A.
Publication year - 2010
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/j.1365-2052.2010.02109.x
Subject(s) - per2 , clock , biology , circadian rhythm , immune system , circadian clock , immunology , cytokine , whole blood , immunity , endocrinology , medicine
Summary The immune system demonstrates regularly recurring rhythmic variation that has important medical and veterinary clinical implications. Emerging evidence supports the existence of a bidirectional immune–circadian relationship during homeostatic challenge. In peripheral blood, circadian rhythmicity manifests in terms of clock gene expression, circulating levels and function of leucocyte cell populations and cytokine production. The involvement of interleukin 6 ( IL6 ) in the transition from innate to acquired immunity is known, and inflammatory mediators can, in turn, phase shift peripheral molecular clocks. This study provides an initial investigation of diurnal variation in circadian clock and immune mediator response to antigenic challenge in the horse. Blood samples were collected at 4‐h intervals at circadian times (CT) 0, 4, 8, 12, 16 and 20 from healthy Thoroughbred fillies maintained under winter photoperiod. Heparinized blood was cultured at 37 °C for 6 h with or without lipolysaccharide (LPS) (1 μg/ml). Cells were harvested by the addition of PAXgene™ RNA stabilizer solution to immediately preserve the RNA profile. Analyses of Taqman qPCR expression data reveal a significant CT X LPS interaction for the canonical clock genes PER2, CRY1, ARNTL, NR1D2 ( P < 0.001, P < 0.05, P < 0.05, P < 0.01 respectively) and the immunomodulatory cytokine IL6 ( P < 0.0001). LPS upregulated IL1B levels ( P < 0.01), but there was no effect of CT. These results confirm that peripheral blood differentially responds to antigenic challenge over the 24‐h cycle, impacting on our understanding of the pathophysiology of inflammatory responses. Further research in this area should provide valuable information regarding the optimum time for drug delivery and vaccination.