The Immune–Pineal Axis

Abstract

The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.

Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis

“…Corticosterone was shown to increase melatonin synthesis in vitro after low noradrenergic stimulation [9,21] and in vivo after mild stress [27], local transpineal perfusion of corticosterone [26] and during chronic inflammation [29]. Our present data show that corticosterone potentiates pineal hormonal production only when the glands are incubated with a β-adrenergic agonist, reinforcing that the pattern of adrenoceptor stimulation is the driving force for the final effect induced by corticosterone on pineal function.…”

“…However, previous literature data show controversial results regarding this crosstalk, indicating both stimulatory and inhibitory effects of glucocorticoids on pineal melatonin synthesis [9,21,22,23,24,25,26,27,28,29]. The present study shows that the pattern of adrenergic activation in the pineal gland regulates the direction of the corticosterone effect on melatonin synthesis (fig.…”

“…Similarly, in vivo data show that perfusion of a high corticosterone concentration [23], or stress-induced plasma corticosterone elevation [24,25], inhibits pineal melatonin synthesis. This contrasts to transpineal infusion of a high corticosterone concentration [26], mild restraint stress in rats [27] or thermic stress in goats [28], which potentiate pineal melatonin production. Likewise, adrenalectomy (ADX) reverses the reduction in the nocturnal melatonin surge induced by intense acute stress [25] but decreases melatonin levels in chronic inflamed mice [29].…”

Участие Эпифиза В Антистрессорном Действии Адаптогенных Средств

“… ñîîòâåòñòâèè ñ íàáëþäåíèÿìè äðóãèõ èññëåäîâà-òåëåé [10] â íàøèõ îïûòàõ õðîíè÷åñêèé áîëåâîé ñòðåññ ïðîâîöèðîâàë îò÷¸òëèâûå èçìåíåíèÿ ýïèôè-çàðíîé àêòèâíîñòè. Ýòî, â ïåðâóþ î÷åðåäü, êàñàëîñü ñîñòîÿíèÿ èíòàêòíûõ êðûñ, ó êîòîðûõ â ïèíåàëîöèòàõ äîñòîâåðíî ïàäàë óðîâåíü ãëèêîãåíà (íà 33,7 ± 3,5 %, p < 0,05) è ðîñëî ÿäåðíî-öèòîïëàçìàòè÷åñêîå ñîîòíî-øåíèå (íà 49,0 ± 2,8 %, p < 0,01).…”

Daily corticosterone rhythm modulates pineal function through NFκB-related gene transcriptional program

“…The interplay between the two hormones has been evaluated in stressful conditions or in models of infection 8–11 . The anti-inflammatory effect of glucocorticoids mediated by activation of transcription programs is triggered by the nuclear translocation of the glucocorticoid receptor (GR) 12 .…”