Decreased expression of CD69 in chronic fatigue syndrome in
relation to inflammatory markers:
evidence for a severe disorder in the early activation of T lymphocytes and
natural killer cells.
Journal: Neuro Endocrinol Lett. 2007 Jul 11;28(4) [Epub ahead
of print]
Authors: Mihaylova I, Deruyter M, Rummens JL, Bosmans E,
Maes M.
Affiliation: MCare4U Outpatient Clinics, Belgium.
NLM Citation: PMID: 17693977
There is some evidence that patients with chronic fatigue
syndrome (CFS) suffer from immune abnormalities, such as
immune activation and decreased immune cell responsivity
upon polyclonal stimili. This study was designed to evaluate
lymphocyte activation in CFS by using a CD69 expression
assay. CD69 acts as a costimulatory molecule for T- and natural
killer (NK) cell activation.
We collected whole blood from CFS patients, who met CDC
criteria, and healthy volunteers. The blood samples were
stimulated with mitogens during 18 h and the levels of activated
T and NK cells expressing CD69 were measured on a Coulter
Epics flow cytometer using a three color immunofluorescence
staining protocol.
The expression of the CD69 activation marker on T cells (CD3+,
CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+)
was significantly lower in CFS patients than in healthy subjects.
These differences were significant to the extent that a significant
diagnostic performance was obtained, i.e. the area under the
ROC curve was around 89%. No differences either in the
number of leukocytes or in the number or percentage of
lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found
between CFS patients and the controls. Patients with CFS show
defects in T- and NK cell activation.
Since induction of CD69 surface expression is dependent on
the activation of the protein kinase C (PKC) activation pathway,
it is suggested that in CFS there is a disorder in the early
activation of the immune system involving PKC.
Not in the mind but in the cell: increased production of
cyclo-oxygenase-2 and inducible
NO synthase in chronic fatigue syndrome.
Journal: Neuro Endocrinol Lett. 2007 Jul 11;28(4) [Epub ahead
of print]
Authors: Maes M, Mihaylova I, Kubera M, Bosmans E.
Affiliation: MCare4U Outpatient Clinics, Belgium.
NLM Citation: PMID: 17693978
Chronic fatigue syndrome (CFS) is a medically unexplained
disorder, characterized by profound fatigue, infectious,
rheumatological and neuropsychiatric symptoms. There is,
however, some evidence that CFS is accompanied by signs of
increased oxidative stress and inflammation in the peripheral
blood. This paper examines the role of the inducible enzymes
cyclo-oxygenase (COX-2) and inducible NO synthase (iNOS) in
the pathophysiology of CFS.
Toward this end we examined the production of COX-2 and
iNOS by peripheral blood lymphocytes (PBMC) in 18 CFS
patients and 18 normal volunteers and examined the
relationships between those inflammatory markers and the
severity of illness as measured by means of the FibroFatigue
scale and the production of the transcription factor nuclear factor
kappa beta (NFkappabeta).
We found that the production of COX-2 and iNOS was
significantly higher in CFS patients than in normal controls.
There were significant and positive intercorrelations between
COX-2, iNOS and NFkappabeta and between COX-2 and
iNOS, on the one hand, and the severity of illness, on the other.
The production of COX-2 and iNOS by PBMCs was significantly
related to aches and pain, muscular tension, fatigue,
concentration difficulties, failing memory, sadness and a
subjective experience of infection.
The results suggest that
a) an intracellular inflammatory response in the white blood cells
plays an important role in the pathophysiology of CFS;
b) the inflammatory response in CFS is driven by the
transcription factor NFkappabeta;
c) symptoms, such as fatigue, pain, cognitive defects and the
subjective feeling of infection, indicates the presence of a
genuine inflammatory response in CFS patients; and
d) CFS patients may be treated with substances that inhibit the
production of COX-2 and iNOS.
Not in the mind of neurasthenic lazybones but in the cell nucleus: patients
with chronic
fatigue syndrome have increased production of nuclear factor kappa beta.
Journal: Neuro Endocrinol Lett. 2007 Jul 11;28(4) [Epub ahead
of print]
Authors: Maes M, Mihaylova I, Bosmans E.
Affiliation: MCare4U Outpatient Clinics, Belgium.
crc.mh@telenet.be.
NLM Citation: PMID: 17693979
There is now some evidence that chronic fatigue syndrome is
accompanied by an activation of the inflammatory response
system and by increased oxidative and nitrosative stress.
Nuclear factor kappa beta (NFkappabeta) is the major
upstream, intracellular mechanism which regulates inflammatory
and oxidative stress mediators. In order to examine the role of
NFkappabeta in the pathophysiology of CFS, this study
examines the production of NFkappabeta p50 in unstimulated,
10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL
PMA (phorbolmyristate acetate) stimulated peripheral blood
lymphocytes of 18 unmedicated patients with CFS and 18
age-sex matched controls.
The unstimulated (F=19.4, df=1/34, p=0.0002),
TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9,
df=1/34, p=0.008) stimulated production of NFkappabeta were
significantly higher in CFS patients than in controls. There were
significant and positive correlations between the production of
NFkappabeta and the severity of illness as measured with the
FibroFatigue scale and with symptoms, such as aches and pain,
muscular tension, fatigue, irritability, sadness, and the subjective
feeling of infection.
The results show that an intracellular inflammatory response in
the white blood cells plays an important role in the
pathophysiogy of CFS and that previous findings on increased
oxidative stress and inflammation in CFS may be attributed to
an increased production of NFkappabeta. The results suggest
that the symptoms of CFS, such as fatigue, muscular tension,
depressive symptoms and the feeling of infection reflect a
genuine inflammatory response in those patients.
It is suggested that CFS patients should be treated with
antioxidants, which inhibit the production of NFkappabeta, such
as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid
and omega-3 fatty acids.