title: Intracerebral interleukin-1beta impairs response to tumor invasion: involvement of adrenal catecholamines.
abstract: Interleukin-1beta (IL-1beta) is released within the brain following stress, trauma, infection, and in specific brain disorders. This centrally acting IL-1beta has recently been shown to impair peripheral immunity. Central administration of IL-1beta suppresses natural killer (NK) cell activity impairs lung clearance of tumor cells and enhances tumor colonization. Using an in vivo model of tumor colonization (lung clearance of NK-sensitive MADB106 adenocarcinoma cells), this study examined the role of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) in mediating these effects. We demonstrate that adrenalectomy significantly attenuated the impaired lung clearance of MADB106 tumor cells induced by intracerebroventricular (i.c.v.) administration of IL-1beta (20 ng). Supplementing adrenalectomized animals with corticosterone did not reinstate the effect. The effect of IL-1beta on lung clearance was blocked by pretreatment with the beta-adrenergic antagonist, nadolol (0.5 mg/kg), but not by the alpha-antagonist phentolamine (5 mg/kg). Peripheral noradrenergic pathways are not implicated given that systemic administration of the noradrenergic neurotoxin, 6-hydroxydopamine, did not block the effect of IL-1beta. Taken together, these findings indicate that IL-1beta impairs lung clearance of MADB106 tumor cells via the actions of adrenal catecholamines, most likely epinephrine, acting at beta-adrenergic receptors in the periphery.
authors.affiliation: Department of Neurobiology and Brain Research Institute, School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. dhodgson@psychology.newcastle.edu.au
authors.forename: D M
authors.initials: DM
authors.lastname: Hodgson
authors.forename: R
authors.initials: R
authors.lastname: Yirmiya
authors.forename: F
authors.initials: F
authors.lastname: Chiappelli
authors.forename: A N
authors.initials: AN
authors.lastname: Taylor
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D003345:Corticosterone / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007111:Immunity, Cellular / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008297:Male; D009248:Nadolol / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000276:immunology*; D016627:Oxidopamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013564:Sympathetic Nervous System / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D018674:Adrenergic Antagonists; D002395:Catecholamines; D007375:Interleukin-1; D009248:Nadolol; D016627:Oxidopamine; D003345:Corticosterone; D010646:Phentolamine