title: Effect of interleukin 1beta on the HPA axis in H1-receptor knockout mice.
abstract: OBJECTIVE
  Circulating cytokines such as interleukin-1 (IL-1), and tumor necrosis factor-alpha as well as lipopolysaccharide (LPS) are potent ACTH secretagogues, acting via stimulation of corticotropin-releasing hormone (CRH) and vasopressinergic neurons in the paraventricular nucleus of the hypothalamus (PVN). Histamine (HA) has been shown to stimulate ACTH secretion in rats, an effect in part mediated by CRH and arginine vasopressin (AVP). We have previously shown that inhibition of neuronal HA synthesis or central blockade of H(1) receptors (H(1)R) decreased the ACTH response to LPS in male rats. To further elucidate the role of neuronal HA in cytokine-induced activation of the HPA axis, we compared the effect of H(1)R knockout on IL-1beta-induced ACTH secretion in adult male mice.
  
  
  RESULTS
  In H(1)R knockout mice, ACTH secretion increased from basal levels of 261 to 492 pmol/l in response to IL-1beta whereas the cytokine-induced ACTH secretion increased from 140 to 406 pmol/l in wild-type mice. Plasma corticosterone (CORT) rose from basal levels of 99 to 831 nmol/l in knockout mice upon IL-1beta stimulation, whereas in wild-type mice CORT levels rose from 112 to 841 nmol/l. There was no significant difference in IL-1beta-stimulated plasma ACTH or CORT levels between wild-type and knockout mice. Furthermore, there was no significant difference in basal or IL-1beta-stimulated hypothalamic levels of histamine and tele-methyl-histamine between wild-type and knockout mice. HDC gene expression was significantly lower in knockout mice than in wild-type mice both under basal and IL-1beta-stimulated conditions, while there were no significant differences in CRH gene expression in the PVN in knockout mice under basal and IL-1beta-stimulated conditions. Increased basal expression of AVP in the PVN of knockout mice was observed in this study compared to wild-type mice.
  
  
  CONCLUSIONS
  We conclude that the lack of the gene for histamine H(1)R does not seem to be crucial for the ACTH and CORT response to IL-1beta, either due to possible functional compensation in the H(1)R knockout mouse or due to activation of pathways other than the neuronal histaminergic system.
authors.affiliation: Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark. ctoftegaard@hotmail.com
authors.forename: C L
authors.initials: CL
authors.lastname: Toftegaard
authors.forename: U
authors.initials: U
authors.lastname: Knigge
authors.forename: A
authors.initials: A
authors.lastname: Kjaer
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: L
authors.initials: L
authors.lastname: Friis-Hansen
authors.forename: J
authors.initials: J
authors.lastname: Warberg
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D003345:Corticosterone / Q000276:immunology / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000276:immunology; D006632:Histamine / Q000276:immunology*; D006640:Histidine Decarboxylase / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D007375:Interleukin-1; D008761:Methylhistamines; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D001127:Arginine Vasopressin; D006632:Histamine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006640:Histidine Decarboxylase; C020404:tele-methylhistamine; D003345:Corticosterone