Intravenous administration of interleukin-1β induces Fos-like immunoreactivity in corticotropin-releasing hormone neurons in the paraventricular hypothalamic nucleus of the rat

It has been shown that acute administration of recombinant human interleukin 1β (IL-1) to rats elicits an activation of the pituitary-adrenal axis. In the present study we investigated immunohistochemically the expression of Fos-like immunoreactivity (Fos-LI) in the hypothalamus of rats following intravenous injection of IL-1. One, 2 and 4 h after IL-1 or physiological saline injections, rats were killed and perfused, and the brains processed for Fos-immunohistochemistry. Dense populations of neurons containing Fos-LI-positive nuclei were found in the paraventricular hypothalamic nuclei (PVH) of IL-1-treated rats. In particular, the dorsal medial parvocellular part, but also some of the other parvocellular subdivisions contained many Fos-LI neurons. Maximal induction of staining was found at a dose of 5 μ/rat after 1 or 2 h survival, while immunostaining had decreased to almost control levels after 4h. No Fos-LI was found in the PVH of control aminals. Double immunocytochemical staining for Fos and corticotropin-releasing hormone (CRH) revealed that Fos-LI was predominantly present in parvocellular CRH-containing neurons of the PVH. The finding that peripherally injected IL-1 induces Fos-LI in hypothalamic CRH neurons strengthens the hypothesis that these neurons are part of the circuitry mediating IL-1-induced activation of the pituitary-adrenal axis.