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

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.