The effects of interleukin‐2 treatment on endothelin and the activation of the hypothalamic–pituitary–adrenal axis

Abstract

Our data demonstrate that cytokines are able to activate the human hypothalamo-pituitary-adrenal axis in vivo. On the basis of the observed time kinetics and in connection with previous findings from in vitro and animal models, we conclude that endothelin may be a link between cytokines and corticotrophin-releasing hormone, most probably functioning as a cytokine-induced neuromodulator controlling pituitary functions.

The Impact of Escitalopram on IL-2-Induced Neuroendocrine, Immune, and Behavioral Changes in Patients with Malignant Melanoma: Preliminary Findings

“…First, in response to IL-2 administration, over time, there appears to be an enhancement of ACTH response. This increasing ACTH secretion is congruent with previous preclinical and clinical studies showing that IL-2 administration is associated with activation of stress-responsive neuroendocrine pathways [corticotropin releasing hormone (CRH) and HPA axis] (Butler et al, 1989;Denicoff et al, 1987;Hanisch et al, 1994;Karanth and McCann, 1991;Katahira et al, 1998;Raab et al, 1999;Raber et al, 1995;Spina et al, 1994). We postulate that this enhanced ACTH response may be related to IL-2-induced dysregulation of glucocorticoid receptor function at the level of the pituitary, hypothalamus, and/or hippocampus (Raison and Miller, 2003a) and possibly due to interactions between glucocorticoid receptors and innate immune signaling pathways and/or activation of T-cell responses involving DNA binding of nuclear factor of activated T cells and activation protein-1.…”

“…As discussed above, activation of stress-responsive neuroendocrine pathways (CRH and HPA) likely contributed, given that ACTH plasma concentrations had a significant association with magnitude of HAM-D score. The release of proinflammatory cytokines implicated in mood regulation, including IL-6 and TNF-alpha (Butler et al, 1989;Raab et al, 1999;Saraya and Balkwill, 1993), during IL-2 therapy likely also contributed to the induction of depressive symptoms. Alterations in metabolism of certain monoamines (eg, serotonin, dopamine, acetylcholine) or receptor function (eg, NMDA) might also have been plausibly involved in IL-2's induction of depressive symptoms (Anisman and Merali, 1999;Lacosta et al, 2000).…”

Interleukin‐2 given to asymptomatic HIV‐infected individuals leads to an exaggerated response of the pituitary gland to the action of CRH

“…Another possibility for the stimulation of the HPA is an IL‐2‐stimulated second mediator such as endotheline as shown in a study with cancer patients. This study, however, was also looking for short‐term effects rather than day to day differences (Raab et al ., 1999).…”

Biomarkers, Fatigue, Sleep, and Depressive Symptoms in Women With Breast Cancer: A Pilot Study

“…Numerous studies have attempted to identify the physiologic mechanisms of cancer treatments that cause side effects such as fatigue (Haylock & Hart, 1979;Jones, Wadler, & Hupart, 1998;Payne, 2002;Payne, Piper, Rabinowitz, & Zimmerman, 2003;Raab et al, 1999;Sephton, Sapolsky, Kraemer, & Spiegel, 2000;Touitou, Bogdan, Levi, Benavides, & Auzeby, 1996). In addition, various theories have been proposed to explain how fatigue occurs (Aistars, 1987;Cleeland, 2001;Grandjean, 1970;Gutstein, 2001;Irvine et al, 1994;Norris, 1982;Payne, 2004;Pickard-Holley, 1991;Piper et al, 1987;Winningham et al, 1994).…”