Circadian immune measures in healthy volunteers: Relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters

Objective: The purpose of this study is to examine the circadian pattern of specific immunologic measures and to compare observed circadian rhythms of these measures with the well-established circadian rhythms of hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Methods: Blood samples were collected every 2 hours for a total of 24 hours from nine healthy volunteers. The blood samples were assayed for hormones and immune measures, including adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and epinephrine. The immune measures included percentage and absolute number of neutrophils, lymphocytes, the lymphocyte subsets CD3+ (T cells), CD4+ (T helper/inducer), CD8+ (T suppressor/cytotoxic), CD56+ (natural killer [NK] cells) and NK cell activity (NKCA). Results: The following immune measures exhibited a significant circadian rhythm: the percentages of neutrophils, CD4+ cells, and CD56+ cells; the absolute numbers of total lymphocytes, CD3+ cells, CD4+ cells, and CD8+ cells; and NKCA. Cross-correlations between the circadian rhythms of selected hormones and immune measures indicated a strong inverse association between the circadian rhythms of cortisol and the different T cell subsets on the one hand, and a strong direct association between the rhythms of cortisol and the percentage of CD56+ and NKCA on the other. Cross-correlations involving the circadian rhythms of norepinephrine and the same immune measures were in general much weaker and statistically nonsignificant. Conclusion: In healthy individuals, both enumerative and functional immune measures exhibit circadian rhythms that seem to be associated most closely with the circadian rhythm of cortisol.