The effects of interleukin 1 beta on the hypothalamic tachykinin, neurokinin A

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that appears to be an integral component of the bidirectional signalling between the immune and central nervous systems. It is produced in the hypothalamus and has been shown to inhibit the hypothalamo-pituitary-gonadal axis and to activate the hypothalamo-pituitary-adrenal axis. IL-1 beta is reported to up-regulate the tachykinin, substance P (SP), in the peripheral nervous system. We have recently observed that members of the hypothalamic tachykinin family including SP, neurokinin A (NKA) and two N-terminal extended forms of NKA (neuropeptides kappa and gamma), inhibit hypothalamic LHRH and pituitary LH release and stimulate adrenal corticosterone secretion. The similarity in the endocrine effects of the tachykinins and the cytokine prompted us to test the hypothesis that IL-1 beta may stimulate the hypothalamic tachykinins, which would then mediate the neuroendocrine effects of IL-1 beta. First, the effects of IL-1 beta on the in vitro release of NKA-like immunoreactivity (NKA-li) from the hypothalamus was examined. Addition of 10 nM IL-1 beta significantly increased NKA-li release from the hypothalami of castrated rats, but not from the hypothalami of intact rats. To identify the site of IL-1 beta action, the effects of intraventricular IL-1 beta (100 ng) on NKA-li levels in various hypothalamic sites of intact and castrated rats were examined. The results showed that IL-1 beta increased NKA-li selectively in the median eminence (ME) and arcuate nucleus (ARC) of castrated rats only.(ABSTRACT TRUNCATED AT 250 WORDS)