TY - JOUR

T1 - Effect of interleukin 1β on the HPA axis in H1-receptor knockout mice

AU - Toftegaard, C. L.

AU - Knigge, U.

AU - Kjær, A.

AU - Watanabe, T.

AU - Friis-Hansen, L.

AU - Warberg, J.

PY - 2002

Y1 - 2002

N2 - Objectives and Methods: Circulating cytokines such as interleukin-1 (IL-1), and tumor necrosis factor-alpha as well as lipopolysaccharide (LPS) are potent ACTH secre-tagogues, 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 H1 receptors (H1R) 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 1R knockout on IL-1β-induced ACTH secretion in adult male mice. Results: In H1R knockout mice, ACTH secretion increased from basal levels of 261 to 492 pmol/l in response to IL-1β 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-1β stimulation, whereas in wild-type mice CORT levels rose from 112 to 841 nmol/l. There was no significant difference in IL-1β-stimulated plasma ACTH or CORT levels between wild-type and knockout mice. Furthermore, there was no significant difference in basal or IL-1β-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-1β-stimulated conditions, while there were no significant differences in CRH gene expression in the PVN in knockout mice under basal and IL-1β-stimulated conditions. Increased basal expression of AVP in the PVN of knockout mice was observed in this study compared to wild-type mice. Conclusion: We conclude that the lack of the gene for histamine H1R does not seem to be crucial for the ACTH and CORT response to IL-1β, either due to possible functional compensation in the H1R knockout mouse or due to activation of pathways other than the neuronal histaminergic system.

AB - Objectives and Methods: Circulating cytokines such as interleukin-1 (IL-1), and tumor necrosis factor-alpha as well as lipopolysaccharide (LPS) are potent ACTH secre-tagogues, 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 H1 receptors (H1R) 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 1R knockout on IL-1β-induced ACTH secretion in adult male mice. Results: In H1R knockout mice, ACTH secretion increased from basal levels of 261 to 492 pmol/l in response to IL-1β 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-1β stimulation, whereas in wild-type mice CORT levels rose from 112 to 841 nmol/l. There was no significant difference in IL-1β-stimulated plasma ACTH or CORT levels between wild-type and knockout mice. Furthermore, there was no significant difference in basal or IL-1β-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-1β-stimulated conditions, while there were no significant differences in CRH gene expression in the PVN in knockout mice under basal and IL-1β-stimulated conditions. Increased basal expression of AVP in the PVN of knockout mice was observed in this study compared to wild-type mice. Conclusion: We conclude that the lack of the gene for histamine H1R does not seem to be crucial for the ACTH and CORT response to IL-1β, either due to possible functional compensation in the H1R knockout mouse or due to activation of pathways other than the neuronal histaminergic system.

KW - Histamine

KW - HPA axis

KW - IL-1β

KW - Knockout mice

UR - http://www.scopus.com/inward/record.url?scp=0043074618&partnerID=8YFLogxK

U2 - 10.1159/000071475

DO - 10.1159/000071475

M3 - Journal article

C2 - 12907841

AN - SCOPUS:0043074618

VL - 10

SP - 344

EP - 350

JO - NeuroImmunoModulation

JF - NeuroImmunoModulation

SN - 1021-7401

IS - 6

ER -