Effects of interleukin-1 on the stress-responsive and -nonresponsive subtypes of corticotropin-releasing hormone neurosecretory axons.

Abstract

Administration of interleukin-1 (IL-1) induces increases in plasma ACTH and glucocorticoids. Numerous experiments have implicated the hypothalamic CRH neurosecretory system in these responses, but have failed to provide evidence for involvement of the ACTH secretagogue vasopressin (VP). The rat CRH neurosecretory system contains two types of cells: VP expressing and VP deficient. Hence, the above findings suggested that IL-1 may selectively activate the VP-deficient subtype of CRH neurosecretory cells. In this study we employed postembedding electron microscopic immunocytochemistry to directly assay IL-1-induced depletion of secretory vesicles from identified VP-expressing and VP-deficient CRH neurosecretory axons. IL-1-induced depletion of secretory vesicles from these axons was correlated with increases in plasma ACTH and decreases in plasma PRL. No dose of IL-1 was found that could selectively activate one subtype of CRH neurosecretory axons; at doses of 0.67 microgram/100 g and above for both IL-1 alpha and IL-1 beta, equal depletion of vesicles from the two subtypes was observed. Similar results were previously found after the injection of bacterial lipopolysaccharide, which induces the release of IL-1 from macrophages. The findings unequivocally establish for the first time that IL-1 activates hypothalamic CRH neurosecretory cells in the absence of surgical stress, anesthesia, disruption of the infundibular area, or administration of toxic drugs. In addition, these data clearly demonstrate that IL-1 induces the release of VP from neurosecretory axons in the portal capillary zone of the external zone of the median eminence. Previous studies have shown that the VP-deficient subtype of CRH neurosecretory axons is not strongly activated by several types of stress; therefore, activation of the system by inflammatory mediators involves mechanisms different from those mediating the stress response.

Effects of Intravenous Administration of Interleukin-1-Beta on the Release of Prostaglandin E₂, Corticotropin-Releasing Factor, and Arginine Vasopressin in Several Hypothalamic Areas of Freely Moving Rats: Estimation by Push-Pull Perfusion

“…Since AVP is one of the non-CRF ACTH secretagogues [28], present and previous [16] data of ours suggest that not only CRF but also AVP may mediate the IL-1P stimulation of ACTH secretion. Although this no tion does not agree with all of the previous reports by oth er investigators [29][30][31][32], the recent report of Whitnall et al [33] is in close accordance with our observation.…”

Sex Differences in the Hypothalamo-Pituitary-Adrenal Axis Response to Inflammatory and Neuroendocrine Stressors

“…Conversely, when we used LPS or SV to stimulate HPA axis function in these animals, the results indicated that LEW/N female rats were hyporesponsive compared with F344/N female rats; the former secreted a decreased amount of ACTH in response to both inflammatory stim uli and, interestingly, this response was similar to the one observed in male LEW/N animals similarly treated. It is accepted that LPS activates macrophages that release cytokines [26,27], these substances in turn activate the hypothalamus to secrete CRH but not AVP [28][29][30]; thus, CRH released into the portal circulation stimulates corticotrope cells. Since we observed a decreased corticotrope response to CRH stimulation in LEW/N vs. F344/N female rats, the in vivo diminished ACTH release after LPS administration could be related, at least in part, to the impaired corticotrope function, probably due to an early inadequate priming of corticotropes by CRH or oth er ACTH secretagogues [1,4].…”

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

“…However, the influence of LPS and cytokines on AVP release remains controversial. 127,136,222,223 In another study in unrestrained conscious sheep, Dadoun et al demonstrated that the activation of the HPA axis after endotoxin administration is associated with an increased release of both CRH and AVP into hypophysial portal blood (HBP). 224 Magnocellular AVP neurons are only initially stimulated, while parvocellular CRH and AVP neurons are stimulated throughout these experiments, as reflected by different AVP levels in portal and jugular blood.…”