Biology Reference
In-Depth Information
12.4.1.4 Effect of Neuroleptics on Immune Function
Some
in vitro
studies have reported that neuroleptics can cause immune activation
[163,164]
, whereas others have demonstrated the opposite effect
[152,159]
. Patients
treated with haloperidol have a positive correlation between CSF IL-10 concentra-
tions and symptom severity, particularly with respect to negative symptoms
[156]
.
Chlorpromazine (CPZ) inhibits TNF- production and protects mice from IL-1 tox-
icity and endotoxin-induced TNF- toxicity
[165,166]
. Studies
in vitro
with mitogen-
stimulated lymphocytes have demonstrated that haloperidol, CPZ, and flupenthixol
inhibit production of IL-2 but not IL-1
[167]
. CPZ also reduces mRNAs for IL-2,
IFN-, and TNF- in human T cells and thymocytes, as well as inhibiting the release
of activating cytokines
in vitro
[168,169]
. Conversely, the concentrations of SIL-2r
are increased by neuroleptic treatment, although this effect was originally thought to
be a consequence of the disorder
[143,148,170-172]
. A significant decrease in SIL-6r
levels has also been noted during antipsychotic therapy
[140,141,151,152,173]
. The
typical antipsychotics (e.g., CPZ and haloperidol) appear to have negative immuno-
regulatory effects, whereas the atypical antipsychotics (e.g., clozapine, risperidone)
have more complex effects on the immune system. Clozapine treatment can reduce to
normal the elevated blood concentrations of TNF- noted in schizophrenic patients
[174]
, and can produce agranulocytosis in some patients
[175]
. A controlled clinical
trial, which administered the COX-2 inhibitor celecoxib or placebo to schizophrenic
patients who were also receiving risperidone, indicated a benefit from celecoxib. The
data showed a significant decrease in total positive and total negative syndrome scale
scores, a significant decrease in negative symptoms
[176]
. Although the magnitude
of improvement was modest, these data add further support for the involvement of
inflammatory processes in the etiology of this disorder, and will encourage further
research into the use of therapies employing immunomodulatory compounds.
12.5 Concluding Remarks
The behavioural effects of inflammatory mediators, such as the cytokines , in response
to an immunological challenge or in the presence of an inherent disorder of the immune
system (such as autoimmune disease) have been examined in detail. These include
sickness behavior, effects on thermoreglation, sleep, ingestion and cognition. The link
between altered immune function and the possible role of inflammatory mediators in
the aetiology of affective disorders such as depression and schizophrenia has also been
examined. This has led to the suggestion that manipulations of the immune system
(such as the use of interleukin receptor antagonists or COX-2 inhibitors) may lead to
novel therapies which would be of benefit in these conditions.
References
1. Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreac-
tivity of the brain: a new view. Immunol Today 1992;13:507-12.
