In his presentation in Bergen on 20th October 2009,
Professor Peter White’s power point slides state about (ME)CFS
that maintaining factors include illness beliefs, the search for
legitimacy, being on benefits, and the diagnostic label, and
that immune or viral measures are NOT involved in the
maintenance of the disorder.
White’s assertion that immune or viral measures are not involved
in the maintenance of the disorder would seem to be a direct
denial of the evidence of two of the world’s leading
immunologists who specialise in ME/CFS, Professors Mary Ann
Fletcher and Nancy Klimas, who recently published yet more
confirmatory evidence of immune dysfunction in the maintenance
of the disorder (Journal of Translational Medicine 2009:7:96:
doi:10.1186/1479-5876-7-96). Their peer reviewed article was
published immediately upon acceptance.
Fletcher and Klimas et al are clear that cytokine abnormalities
are common in (ME)CFS and that the cytokine changes observed are
more likely to be indicative of immune activation and
inflammation, rather than specific for (ME)CFS, as people with
fibromyalgia, Gulf War Illness, rheumatological disorders and
multiple sclerosis may also have similar cytokine patterns.
The authors do, however, demonstrate that several of the
abnormal cytokines show promise as potential biomarkers for (ME)CFS.
As Fletcher and Klimas et al point out:
“CFS studies from our laboratory and others have
described cytokine abnormalities. Other studies
reported no difference between (ME)CFS and controls.
However, methodologies varied widely and few studies
measured more than 4 or 5 cytokines. Multiplex
technology permits the determination of cytokines
for a large panel of cytokines simultaneously with
“In this study, 10 of 16 cytokines examined showed good to
fair promise as biomarkers. However, the cytokine
changes observed are likely to be more indicative of
immune activation and inflammation…Many of the
symptoms are inflammatory in nature."
“There is a considerable literature describing
immune dysfunction in (ME)CFS."
“The goal of this study was to determine if, using
new technology, plasma cytokines had sufficient
sensitivity and specificity to distinguish (ME)CFS
cases from age-matched healthy controls….Amounts of
cytokines in plasma or serum are often below the
level of detection in traditional ELISA assays."
"The availability of sensitive multiplex technology
permitted the determination of 16 cytokines
simultaneously…In the (ME)CFS cases, we found an
unusual pattern of the cytokines that define the CD4
“Pro-inflammatory cytokines: A significant elevation
in the relative amounts of 4 of 5 pro-inflammatory
cytokines in peripheral blood plasma of patients
with (ME)CFS was found when compared with the
controls. In cases, lymphotoxin (LT)awas elevated by
257% and IL-6 by 100% over the controls."
“TH2 cytokines: Both interleukin (IL)-4 and IL-5 were
elevated in (ME)CFS, with the median of IL-4 (being)
240% and of IL-5 (being) 95% higher in cases than
“Anti-inflammatory cytokines: IL-3 was significantly
lower in (ME)CFS patients. “TH1 cytokines: IL-12 was
significantly elevated (120%) and IL-15 decreased
(15%) in cases compared to controls."
“IL-8 (CXCL8): this chemokine was 42% lower in the (ME)CFS
“Along with the TH1 abnormalities, we found up-regulation
of TH2 associated cytokines, IL-4 and IL-5, in the (ME)CFS
subjects. Allergy is common in (ME)CFS cases. Years
ago, Straus et al reported >50% atopy in 24 CFS
“The probability of chronic inflammation in (ME)CFS
patients is supported by the elevation of four
members of the pro-inflammatory cytokine cascade ,
LTa, IL-1a, IL-1b and IL-6, in the (ME)CFS samples
compared to controls."
“Interleukin-13, associated with inhibitory effects
on inflammatory cytokine production, was lower in
cases compared to controls."
“The inflammatory mediator IL-8 (a chemokine known as
CXCL8) known to be responsible for migration and
activation of neutrophils and NK cells was decreased
in plasma of (ME)CFS patients."
“The observations of abnormal cytokine patterns in (ME)CFS
patients support the reports of retrovirus
“Recently, DNA from a human gammaretrovirus,
xenotropic murine leukaemia virus-related virus
(XMRV) was found in the PBMC of 68 of 101 patients
compared to 8 of 218 healthy controls.
Patient–derived, activated PBMC produced infectious
XMRV in vitro. Both cell associated and cell-free
transmission of the virus to uninfected primary
lymphocytes and indicator cell lines was possible."
“The decreased natural killer (NK) cell cytotoxic
and lymphoproliferative activities and increased
allergic and autoimmune manifestations in (ME)CFS
would be compatible with the hypothesis that the
immune system of affected individuals is biased
towards a T-helper (TH) 2 type, or humoral
immunity-orientated cytokine pattern."
“The elevations in LTa, IL-1a, IL1b and IL-6 indicate
inflammation, likely to be accompanied by
autoantibody production, inappropriate fatigue,
myalgia and arthralgia, as well as changes in mood
and sleep patterns."
This study is among the first in the (ME)CFS
literature to report the plasma profiles of a
reasonably large panel of cytokines assessed
simultaneously by multiplex technique."
“Cytokine abnormalities appear to be common in (ME)CFS.
The changes from the normal position indicate immune
activation and inflammation."
“The results imply a disorganised regulatory pattern
of TH1 function, critical to antiviral defence.“
“The results from this study support a TH2 shift,
pro-inflammatory cytokine up-regulation and
down-regulation of important mediators of cytotoxic
Since it is now unequivocal that people with (ME)CFS show
markers of inflammation, what will be the impact on the Wessely
School’s MRC PACE Trial that is predicated on the assumptions of
deconditioning, on the “perception” of effort and on aberrant
illness beliefs and whose participants are instructed about