Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs

Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebroventricular or intravenous route, there was a marked increase in the adrenal cortisol secretion elicited by a subsequent antigenic challenge (whether this was delivered via the central or peripheral route). Comp.48/80, a mast cell secretagogue, also increased cortisol secretion when administered intracerebroventricularly. Pretreatment (intracerebroventricularly) with anti-corticotropin–releasing factor antibodies or a histamine H₁ blocker, but not an H₂ blocker, attenuated the evoked increases in cortisol. These data show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via centrally released histamine and corticotrophin-releasing factor. On the basis of these data, we suggest that intracranial mast cells may act as an allergen sensor, and that the activated adrenocortical response may represent a life-saving host defense reaction to a type I allergy.