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      Interleukin-1α and Interleukin-1β Stimulate Adrenocorticotropin Secretion in the Rat through a Similar Hypothalamic Receptor(s): Effects of Interleukin-1 Receptor Antagonist Protein

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      S. Karger AG

      Median eminence, intracerebral

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          Numerous reports have demonstrated that interleukin-1 β (IL-1β) is a potent secretagogue for adrenocorticotropin (ACTH) and that IL-1α appears to be considerably less efficacious. To clarify apparent differences in the potency of IL- 1α vs. -β on ACTH secretion from a functional perspective, the IL-1 receptor antagonist protein, IRAP, was utilized. Following administration to rats either intravenously (i.v.) or adjacent to the median eminence (intra-ME), IL-1β was approximately 8-fold more potent than IL-1α. IRAP, delivered i.v. or intra-ME, inhibited ACTH secretion due to the administration of IL-1α or -β by the corresponding route. Similar amounts of IRAP were required to attenuate ACTH responses to approximately equieffective i.v. doses of IL-1α (200 ng) or -β (25 ng): IC50 for IRAP inhibition of IL-1α vs. -β was approximately 2.5 or 5.5 µg, respectively. At these IC50 doses, the ratios of IRAP/IL-1 were 12.5 and 220 for IL-1α vs. -β, respectively. These ratios are compatible with mediation by a type I-like IL-1 receptor. To compare these properties of the central IL-1 receptor to a peripheral type I IL-1 receptor in the same species, the IL-1 -enhanced rat thymocyte comitogenesis assay was utilized. Thymocyte proliferation in response to equieffective doses of IL-1α or -β was similarly inhibited by IRAP: approximate IC50 for inhibition of IL-1α vs. -β was 12.5 or 25 ng/ml, respectively. Relative to the dose of IL-1α and -β (5 ng/ml), these amounts of IRAP are within the range required to inhibit (1) the ACTH response to IL-1 in rats, reported herein, and (2) type I IL-1 receptor-mediated responses in peripheral tissues from other species. Thus, the ACTH responses to both IL-1α and IL-1β may be mediated through a central type I-like IL-1 receptor(s), which appears to be similar to the peripheral rat type I receptor. IRAP was effective at inhibiting ACTH secretion stimulated by IL-l when these agents were administered i.v. or into the hypothalamic median eminence, suggesting that type I-like IL-l receptors are present in the median eminence where they are readily accessible to modulation by circulating IL-l.

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          Author and article information

          S. Karger AG
          08 April 2008
          : 57
          : 1
          : 14-22
          Endocrine Neuroscience Laboratories, Minneapolis Medical Research Foundation and the Departments of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, Minn., USA
          126336 Neuroendocrinology 1993;57:14–22
          © 1992 S. Karger AG, Basel

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          Pages: 9
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