Biology Reference
In-Depth Information
lethargy and depressed and irritable mood 24-48 hours prior to recurrence of skin
lesions. Thus, patients' neuropsychiatric symptoms parallel their response to immu-
nological challenge, of which cytokine production is an integral part. Patients treated
with IFN- for chronic viral hepatitis or malignant diseases also exhibit depressive
symptoms.
12.3.3 Postinfective Fatigue and Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS) typically follows relatively minor influenza-like
or mononucleosis-like illnesses. It is characterized by the presence of chronic and
disabling fatigue, in the absence of neurophysiological evidence of actual muscle
fatigue or neuromuscular abnormalities
[48]
; and by neuropsychiatric symptoms such
as sleep disturbance, impaired concentration and memory, mood changes, headaches,
and musculoskeletal pain
[49,50]
. It manifests many of the symptoms of atypical
depression, and 21-47% of CFS patients subsequently experience major depressive
episodes
[51]
. Although extensive studies have been carried out on immunological,
neuroendocrine, neurological, and psychological function in this disorder
[49,52]
,
it remains to be resolved whether this is a nonspecific disorder which is present
during different disease states, or whether particular subsets of CFS with specific
pathophysiological characteristics can be identified
[50,53]
. Of particular relevance
to the possible involvement of cytokines in this disorder are findings that the symp-
toms of CFS are similar to those of sickness behavior or the side effects noted dur-
ing the therapeutic administration of cytokines
[19,54]
. Many patients exhibit CFS
following an infective illness, and there is evidence that in these individuals there is
a persistent low-level activation of the immune system. This includes a reduction in
delayed hypersensitivity skin responses, impaired lymphocyte responses to mitogens,
depressed natural killer (NK) cell activity, increased activity of activation mark-
ers, and the presence of autoantibodies to insoluble cellular antigens
[49,55-57]
. It
has therefore been suggested that the symptoms of CFS are due to enhanced CNS
cytokine production and release in genetically predisposed individuals in response
to antigenic challenge
[49,58]
. However, studies involving the determination of
absolute concentrations of cytokines in the sera have failed to detect any differences
between patients with CFS and controls
[58-61]
. Nevertheless, studies on the release
of cytokines from mononucleocytes
in vitro
have demonstrated increased IFN- pro-
duction in response to viral antigen
[62]
and increased endotoxin-stimulated release
of IL-1, IL-6, and TNF- in patients with CFS
[58]
. It has also been suggested that
the neuropsychiatric symptoms noted in CFS could be due to altered cytokine pro-
duction by glial cells in the CNS. However, this evidence was obtained from patients
who already had well-documented neuropathology, including those with multiple
sclerosis, HIV infection, and Alzheimer's disease.
12.3.4 Systemic Autoimmune Diseases
Systemic autoimmune diseases are often associated with neuropsychiatric phenomena.
However, evidence that these behavioral effects may be due to direct CNS pathology
