Intracerebral interleukin-1β impairs response to tumor invasion: Involvement of adrenal catecholamines

Interleukin-1β (IL-1β) is released within the brain following stress, trauma, infection, and in specific brain disorders. This centrally acting IL- 1β has recently been shown to impair peripheral immunity. Central administration of IL-1β 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-1β (20 ng). Supplementing adrenalectomized animals with corticosterone did not reinstate the effect. The effect of IL-1β on lung clearance was blocked by pretreatment with the β-adrenergic antagonist, nadolol (0.5 mg/kg), but not by the α-antagonist phentolamine (5 mg/kg). Peripheral noradrenergic pathways are not implicated given that systemic administration of the noradrenergic neurotoxin, 6-hydroxy-dopamine, did not block the effect of IL- 1β. Taken together, these findings indicate that IL-1β impairs lung clearance of MADB106 tumor cells via the actions of adrenal catecholamines, most likely epinephrine, acting at β-adrenergic receptors in the periphery.