Acute stimulation of the hypothalamic-pituitary-adrenal axis by IL-1ß, TNFα and IL-6: A dose response study

Abstract

We investigated the effects of i.v. and intracerebroventricular (i.c.v) administration of increasing doses of recombinant human IL-1 beta, TNF alpha and IL-6 on plasma corticosterone (B) levels in rats. Rats were equipped with a jugular cannula for repeated blood sampling anda subgroup of rats also received an i.c.v implanted cannula. I.v. administration of IL-1 beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta and IL-6 induced a significant dose-dependent increase in plasma B levels, whereas i.c.v injection of TNF alpha in doses up to 1000 ng/rat was not effective. I.v. pretreatment of rats with anti-CRH antiserum had no significant overall effect on the plasma B response to i.v. administered IL-1 beta (500 and 3000 ng/rat), whereas the plasma B response to i.v. TNF alpha or IL-6 administration (3000 ng/rat) were significantly reduced. I.v. pretreatment of the animals with recombinant human IL-1 receptor antagonist (IL-1ra) significantly blocked the plasma B response to i.v. treatment with IL-1 beta, whereas the TNF alpha- and IL-6-induced increases in plasma B levels were not affected. Our data show that 1) i.v. administration of IL-beta, TNF alpha or IL-6 and i.c.v administration of IL-1 beta or IL-6 dose-dependently stimulate the HPA axis; 2) when given i.v. or i.c.v, IL-1 beta is more powerful than TNF alpha and IL-6 in activating the HPA axis; 3) endogenous CRH is involved in the activation of the HPA axis by acute i.v. administration of TNF alpha and IL-6. It is most likely that in case of i.v. treatment with IL-1 beta a CRH-independent mechanism is involved. This study provides no arguments for the involvement of endogenous IL-1 in TNF alpha- or IL-6-induced activation of the HPA axis.

Central obesity, depression and the hypothalamo–pituitary–adrenal axis in men and postmenopausal women

“…7 ± 9 We did not ®nd a simple relationship between basal IL-6 levels and CRH responses. Previous work has suggested a close relationship between IL-6 and ACTH circadian rhythm 28 and IL-6 administration has been shown to activate the HPA axis both in animals 11,12 and in humans. 10 Excessive alcohol consumption has been shown to blunt the ACTH and cortisol responses to CRH 29 and impair dexamethasone suppression of plasma cortisol.…”

Interleukin-12 p40 Gene Expression Is Induced in Lipopolysaccharide-Activated Pituitary Glands in vivo

“…Activation of the HPA axis by proinflammatory cytokines provokes the release of glucocorticoids which, in turn, prevent the continuing immune-inflammatory response [1]and thereby regulates a homeostatic neuroendocrine-immune regulatory loop. For example, proinflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α), are expressed in HPA axis tissues [2, 3, 4]and stimulate the release of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), and corticosterone [5, 6, 7, 8, 9, 10]. This indicates that proinflammatory cytokines play an important role in maintaining neuroendocrine-immune homeostasis through the HPA axis.…”

Neuroendocrine-Immune Interactions and Starvation in Mucosal Immunity and Mucosal Inflammation

“…In recent years, our understanding of the interactions between the hypothalamic-pituitary-adrenal (HPA) axis and immune-mediated inflammatory reactions has expanded [37,41]. The neuroendocrine and immune systems communicate bidirectionally, and this bidirectional communication plays an essential role in modulating the adequate response of the HPA axis to the stimulatory influence of interleukins and stress-related mediators [12,37,42].…”

“…The hypothalamus seems to be an important site of IL-1 on the HPA axis, thereby inducing corticotropin-releasing factor (CRF) secretion, followed by adrenocorticotropic hormone (ACTH) and glucocorticoid secretion (Fig. 2) [37,41].…”

“…Inflammatory mediators, such as inflammatory cytokines, act either directly or indirectly to increase the production of hormones in the hypothalamuspituitary-adrenal axes [37,41], and stress responses may modulate the immuno-neuroendocrine interaction [12]. Leptin, an adipose hormone, regulates body weight at the hypothalamic level and also engages in the immunoinflammatory and neuroendocrine pathways, leading to the maintenance of homeostasis of these two different physiologic pathways [9,11].…”