In:
Neuroimmunomodulation, S. Karger AG, Vol. 8, No. 3 ( 2000), p. 154-164
Abstract:
Although acute stress has been reported to suppress natural killer cell activity (NKA) and host resistance to metastasis, it is unclear whether the sympathetic nervous system (SNS) has a role in these effects. The current study in Fischer 344 rats assessed the involvement of adrenal catecholamines and β 〈 sub 〉 1 〈 /sub 〉 - and β 〈 sub 〉 2 〈 /sub 〉 -adrenoceptors in mediating these deleterious effects of swim stress. In addition to assessing the number and activity of NK cells following swim stress, we used a tumor model based on the MADB106 mammary adenocarcinoma line: this syngeneic tumor metastasizes only to the lungs, and its lung tumor retention (LTR) and metastatic colonization are highly sensitive to NKA. The findings indicate that stress increased both LTR, assessed 24 h after inoculation, and the number of lung metastases, counted 3 weeks later. These effects were attenuated or completely abolished by the ganglionic blocker chlorisondamine (3 mg/kg i.p.), by adrenal demedullation, by a selective β-adrenergic antagonist (nadolol, 0.4 mg/kg), and additively by a selective β 〈 sub 〉 1 〈 /sub 〉 - (atenolol, 1–6 mg/kg) and a selective β 〈 sub 〉 2 〈 /sub 〉 -antagonist (either butoxamine 4–32 mg/kg or ICI-118,551 0.3–8 mg/kg). Stress also suppressed NKA, and adrenal demedullation prevented this suppression. Administration of adrenaline (0.1–1 mg/kg) or of a β-adrenergic agonist (metaproterenol, 0.8 mg/kg), in physiologically relevant doses, suppressed NKA in a dose-dependent manner, and increased LTR to levels characteristic of swim stress. Taken together, these findings suggest that acute stress, by releasing catecholamines from the adrenal glands and activating β 〈 sub 〉 1 〈 /sub 〉 - and β 〈 sub 〉 2 〈 /sub 〉 -adrenoceptors, suppresses NKA and consequently compromises resistance to NK-sensitive metastasis.
Type of Medium:
Online Resource
ISSN:
1021-7401
,
1423-0216
Language:
English
Publisher:
S. Karger AG
Publication Date:
2000
detail.hit.zdb_id:
1483035-8
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