Clinical trial NCT00498862: Catecholamines Can Attenuate Intermittent Hypoxia-Induced Expression of TNF in Human Monocytes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Healthy
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2007-07-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: DEFINED_POPULATION
Time perspective: OTHER

Brief summary: Specific aim To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients (2). To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.

(3). To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression

Detailed description: Obstructive sleep apnea syndrome (OSAS) is a common disease, which occurs in 4% middle-aged men and 2% middle-aged women. The characteristic of OSA is recurrent collapse of upper airway during sleep, which results in intermittent hypoxia and sympathetic activation. Cardiovascular complications associated with OSA include artherosclerosis, hypertension, coronary artery disease and congestive heart failure. Several inflammatory mediators including C-reactive protein (CRP), oxidative stress, adhesion molecules, vascular endothelial growth factor and proinflammatory cytokines, were found to be elevated in OSA, which attribute the developments of cardiovascular diseases in OSA. Our data showed serum levels of TNF were higher in OSA patients than in control subjects. And serum levels of TNF were inversely correlated with the lowest pulse oxygen saturation. After one-month CPAP treatment, serum of TNF could significantly go down. This finding suggested TNF was a good biomarker in studying OSA associated cardiovascular complications.

The presentations of sympathetic hyperactivity in OSA include hypercatecholaminemia and elevated sympathetic tone of peripheral nerve. Hypercatecholaminemia is known for attributing to the development of cardiovascular diseases. Our data showed plasma levels of both epinephrine and norepinephrine were higher in OSA patients than in control subjects. And the elevated catecholamine could go down after one-month CPAP treatment. Meanwhile, our data also showed the plasma levels of catecholamine were highly correlated with serum levels of TNF.

In vivo studies showed both epinephrine and norepinephrine could potentiate LPS-induced expression of TNF through 2 adrenergic receptors. However, the effect of catecholamine on TNF production in human monocytes in the hypoxic microenvironment has never been studied. Our preliminary data showed epinephrine had no effect on TNF expression in human monocyte cell line U937 under normoxic condition but could attenuate the TNF expression under hypoxic condition. Therefore, we hypothesize that catecholamines can modulate intermittent hypoxia induced TNF and further affect the developments of cardiovascular complications in OSA. In this project, we'll use peripheral blood monocytes from healthy subjects and OSA patients as the target cells, which were serially treated with catecholamine  or b antagonists in both normoxic and hypoxic microenvironments, to achieve the following 3 objectives:

1. . To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients
2. . To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.
3. . To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression

Eligibility criteria: Inclusion Criteria:

* Healthy volunteer

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan Univerisity Hospital
name: Peiln Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Peilin Lee, M.D.
role: PRINCIPAL_INVESTIGATOR
References: