The primary objective of the study is to assess the function and effect of deiodinase type 3 in PMN*s and the mechanisms behind its induction following activation of these cells.
ID
Source
Brief title
Condition
- White blood cell disorders
- Thyroid gland disorders
- Ancillary infectious topics
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are changes in the amount of D3 protein, D3 activity,
bacterial killing capacity and subcellular localisation of D3 in activated
versus non-activated leukocytes.
Secondary outcome
n.v.t.
Background summary
Illness and infection are known to induce profound changes in thyroid hormone
metabolism. These changes are collectively known as Non-Thyroidal Illness
Syndrome (NTIS) and are characterized by a decrease in systemic thyroid hormone
levels. NTIS occurs in a wide variety of diseases including myocardial
infarction, acute stroke and critical illness. It is seen in 70% of
hospitalized patients and is correlated with disease severity and outcome.
Besides changes in systemic thyroid hormone levels, there is increasing
evidence for local changes in thyroid hormone metabolism in specific tissues
and cell types during illness. One of these cells is polymorphonuclear
leukocytes (PMNs), one of the white blood cell subtypes. Activated leukocytes
have long been known to degrade thyroid hormone. More recently, animal models
have shown that in both acute infection and chronic inflammation, leukocytes
express deiodinase type 3 (D3), an enzyme that inactivates thyroid hormone. D3
knock-out mice have impaired bacterial clearance compared to wildtype mice
suggesting that D3 is a major determinant of the bacterial killing capacity of
leukocytes during infection. The ability of leukocytes to phagocytose and kill
pathogens is of paramount importance during infection and defects in this
bacterial killing machinery can severely affect clinical outcome.
Study objective
The primary objective of the study is to assess the function and effect of
deiodinase type 3 in PMN*s and the mechanisms behind its induction following
activation of these cells.
Study design
The study is an observational laboratory study on leukocytes isolated from
venous blood of healthy volunteers
Study burden and risks
Vena puncture has a risk of mild local discomfort and bruising.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers:
1. Aged >=18
2. Willing and able to provide signed informed consent prior to study-related procedures.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:;1. History of haematological diseases
2. Fever or other symptoms of infection during the past 7 days.
3. Use of medication that could affect haematological parameters or neutrophil function as specified by the Farmacotherapeutisch Kompas (http://www.fk.cvz.nl)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48692.018.14 |