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 andto compare observed circadian rhythms of these measures with the well-established circadian rhythms ofhypothalamic-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. Theblood samples were assayed for hormones and immune measures, including adrenocorticotropic hormone(ACTH), cortisol, norepinephrine, and epinephrine. The immune measures included percentage and absolutenumber 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 ofneutrophils, CD4+ cells, and CD56+ cells; the absolute numbers of total lymphocytes, CD3+ cells, CD4+cells, and CD8+ cells; and NKCA Cross-correlation. s between the circadian rhythms of selected hormones andimmune measures indicated a strong inverse association between the circadian rhythms of cortisol and thedifferent T cell subsets on the one hand, and a strong direct association between the rhythms of cortisol andthe percentage of CD56+ and NKCA on the other. Cross-correlations involving the circadian rhythms ofnorepinephrine and the same immune measures were in general much weaker and statistically nonsignificant.Conclusion: In healthy individuals, both enumerative and functional immune measures exhibit circadianrhythms that seem to be associated most closely with the circadian rhythm of cortisol.Key words: circadian, cortisol, norepinephrine, T cells, NK cells, psychoneuroimmunology.INTRODUCTION