The interleukin-1 type I receptor is expressed in human hypothalamus

Several lines of evidence suggest that interleukin-1 (IL-1) acts directly o n the central nervous system, probably within the hypothalamus, causing eff ects such as fever, activation of the immune response and sickness behaviou r, IL-1 has also been shown to be involved in the aetiology of several neur onal diseases, including neurodegeneration, stroke and Alzheimer's disease. However, the question as to whether the full-length type I IL-1 receptor ( IL-1RI) is expressed in the human hypothalamus has yet to be addressed. Usi ng the polymerase chain reaction, we cloned a full-length cDNA encoding the human hypothalamic IL-1RI from human hypothalamic cDNA. The DNA sequence o f the human hypothalamic receptor was identical to that of the human fibrob last IL-1RI. The IL-1RI receptor protein was detected in astrocytes of norm al human hypothalamic brain sections using immunocytochemical techniques. T o ascertain that the cloned receptor was functional, Chinese hamster ovary (CHO) cells were transfected with a plasmid vector containing the IL-1RI co ding region. IL-1RI-mediated-signal transduction was assessed by microphysi ometry and activation of p38 MAP (mitogen-activated protein) kinase, We rep ort the first demonstration that both the type I IL-1 transcript and the pr otein are expressed in the human hypothalamus. The receptor was expressed i n a stable CHO cell line, providing a tool with which to embark on a thorou gh analysis of the signalling mechanisms mediated by IL-1 via this receptor .