Circadian Secretions of IL-2, IL-12, IL-6 and IL-10 in Relation to the Light/Dark Rhythm of the Pineal Hormone Melatonin in Healthy Humans

Abstract

It has been demonstrated that cytokine activities are under neuroendocrine control, recently mainly exerted by the pineal gland through the circadian secretion of its main hormone melatonin (MLT). It is mainly released during the night, but at present it is still unclear which relation exists between MLT and the circadian secretion of cytokines. This study was performed to evaluate the circadian secretion of IL-2, IL-6, IL-10 and IL-12 in relation to that of MLT. The study included 10 healthy volunteers whose venous blood samples were collected at 8 a.m., noon, 4 p.m., 8 p.m., 1 a.m. and 4 a.m. The mean levels of MLT were significantly higher during the night than during the light phase of the day. Similarly, IL-2 mean levels significantly increased during the night. IL-6 mean values were higher during the light period of the day without, however, any significant differences with respect to the nocturnal mean levels. Finally, no substantial circadian variation was seen in IL-10 and IL-12 mean concentrations. These results show that IL-2 secretion increases during the night, concomitantly to that of the pineal hormone MLT, whereas there is no evidence of a circadian secretion for the other cytokines. Since the pineal gland has been proven to stimulate IL-2 endogenous production, the nocturnal increase in IL-2 blood concentrations could depend at least in part on the promoting action of MLT, whose release increases during the dark period of the day.

Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls

“…This is a somewhat imprecise classification, grouping cytokines from results of experimentally and statistically heterogeneous previous studies. Another limitation is that both blood samples and EEG measurements were taken at varying hours of the day, between 8:00 and 18:00 h. Therefore, an influence of circadian rhythmicity on the levels and effects of cytokines cannot be excluded [50,51]. The temporal resolution of EEG and cytokine measures and the extent to which they may be linked to changes in brain arousal are also disparate.…”

T cells and aging update February 1999

“…In addition, cytokine secretion may be affected by other (non-pathological) parameters such as exercise, as reported by Shinkai et al (205), or possibly by time of day of blood collection because of circadian rythm in cytokine secretion (206). It was nonetheless anticipated that when data became available using donors selected according to the strict standard criteria of the SENIEUR protocol (207)), results on cytokine secretion and other immunogerontological parameters would become more reproducible.…”

Untitled

“…Little is known about the molecular mechanism by which melatonin drives the clock gene feedback loops in the SCN. In addition, the nocturnal increase in the circadian secretion of the cytokine IL-2 and its immunobiological activity are under melatonin control during the dark period 45 .…”