| First Author | Liège S | Year | 2000 |
| Journal | Neuroimmunomodulation | Volume | 7 |
| Issue | 4 | Pages | 189-94 |
| PubMed ID | 10810251 | Mgi Jnum | J:62433 |
| Mgi Id | MGI:1858872 | Doi | 10.1159/000026438 |
| Citation | Liege S, et al. (2000) Activation of the hypothalamic-pituitary-adrenal axis in IL-1 beta-converting enzyme-deficient mice. Neuroimmunomodulation 7(4):189-94 |
| abstractText | Interleukin-1beta (IL-1beta) plays a key role in immune, behavioral and neuroendocrine responses to inflammation or infection. IL-1beta could also be involved in the response of the hypothalamic-pituitary-adrenal (HPA) axis during stress. Mature IL-1beta derives from a 31-kD precursor (pro-IL-1beta) that is processed by IL-1beta-converting enzyme (ICE). Mice in which the ICE gene has been nullated by homologous recombination were used to investigate the role of IL-1beta in the HPA axis response. Plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) in response to an intraperitoneal injection of 5 microg lipopolysaccharide (LPS) were similar in ICE-deficient mice and wild-type (WT) controls. In contrast, plasma ACTH response to restraint or to 200 ng of rat recombinant IL-1beta (rrIL-1beta) was higher in ICE-deficient mice as compared to WT animals. This hyperreactivity of the HPA axis in ICE knockout mice appears not to be related to the production of plasma IL-1beta or IL-6, which was similar to that of WT mice after rrIL-1beta injection. After lipopolysaccharide, ICE-deficient mice exhibited a smaller increase in plasma-immunoreactive IL-1beta and IL-6 as compared to WT controls. After restraint stress neither increase in plasma IL-1beta nor IL-6 was observed. The mechanisms responsible for the increased reactivity of the HPA axis in ICE-deficient mice may result from a higher sensitivity of the HPA axis to inflammatory cytokines or to cleavage products of pro-IL-1beta processed by non-ICE proteases. Copyright 2000 S. Karger AG, Basel |
