Interleukin‐1β Release in the Supraoptic Nucleus Area During Osmotic Stimulation Requires Neural Function

Interleukin (IL)‐1β is present throughout the magnocellular neuroendocrine system and co‐depletes with oxytocin and vasopressin from the neural lobe during salt‐loading. To examine whether IL‐1β is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser‐induced fluorescence detection to quantify cytokine in 5‐min dialysates collected before (0–180 min; basal), and after (180–240 min), hypertonic saline injected s.c. (1.5  m NaCl). Osmotic release of IL‐1β was compared after inhibiting local voltage‐gated channels for Na + (tetrodotoxin) and Ca 2+ (cadmium and nickel) or by reducing intracellular Ca 2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL‐1β + ) and microglia (OX‐42 + ). Under conditions of microdialysis, the basal release of IL‐1β + in the SON area was measurable and stable (pg/ml; mean ± SEM) from 0–60 min (2.2 ± 0.06), 60–120 min (2.32 ± 0.05) and 120–180 min (2.33 ± 0.06), likely originating locally from activated microglia (OX42 + ; IL‐1β + ; ameboid, hypertrophied) and magnocellular neurones expressing IL‐1β. In response to osmotic stimulation, IL‐1β increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca 2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage‐gated Na + and Ca 2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL‐1β in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones.