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the supernatants of whole-blood cell cultures, whereas the TNF- decrease was only
partially prevented. Interestingly, HPX and propranolol also diminished the cell inva-
sion into the cerebrospinal fluid (CSF)
[49]
.
Moreover, we could show that intra-cerebroventricular and intra-hypothalamic
infusion of IL-1 (but not TNF-) dramatically increased neutrophil counts, whereas
lymphocytes dropped. Blocking the HPA axis by HPX abolished the neutrophilia,
although the lymphopenia remained unchanged. Furthermore, application of propra-
nolol prevented the decrease of lymphocytes and diminished the neutrophilia. All
parameters were normalized within 48 hours after termination of infusion
[50]
.
Additionally, we were able to show in a rat model that increased intracranial pres-
sure leading to sympathetic activation rapidly induces an impressive systemic IL-10
release. This effect could be blocked by the -adrenoreceptor antagonist propranolol
[41]
. Elenkov et al. demonstrated that NE and epinephrine suppressed IL-12 produc-
tion in a dose-dependent fashion. However, at physiological concentrations, both cat-
echolamines dose-dependently increased the production of IL-10. The effects of either
catecholamine on IL-12 or IL-10 secretion were blocked completely by propranolol
[51]
. These findings also support the hypothesis that the central nervous system may
regulate IL-12 and IL-10 secretion and, hence, the Th1/Th2 balance, via the SNS.
Through our clinical investigations, we could also show that brain-injured patients
have high IL-10 plasma levels immediately after the acute event. This correlated with
signs of increased intracranial pressure and sympathetic activation, as well as with an
increased risk of infectious complications
[41,52]
. We made similar observations of
patients after neurosurgical procedures, where we could show that a local inflammation
in the CSF with high levels of IL-6 and IL-8 was associated with a monocytic deactiva-
tion, with a decreased expression on human leukocyte antigen, serotype DR (HLA-DR)
molecules and an increased risk of developing infectious complications
[53,54]
.
8.3 Conclusions
In summary, catecholamines and acetylcholine may control local and systemic
immune response during all phases of inflammation. In detail, afferent somatosen-
sory nerves, including the vagus, are able to recognize various signals of things that
could threaten the organism. The resulting information may initiate an inflammatory
response (neurogenic inflammation) via a spinal reflex. Furthermore, depending on
the signal type, an additional immunological inflammation may occur. The released
pro-inflammatory cytokines may again affect somatosensory nerves and signal the
brain that a local inflammatory reaction has occurred. This may activate inhibitory
neuroimmune pathways such as the HPA axis, the SNS, and the vagus to support
a local anti-inflammatory response. However, if inflammation cannot be confined
locally, cytokines may spill over into the blood and induce a SIRS and septic shock.
In this situation, blood cytokines may directly affect the brain and induce a central
CARS in order to restore homeostasis. In addition, the delicate balance between pro-
and anti-inflammatory responses is influenced by the mind: psychological stress can
shift the immune system to one side with consequences for the immune status. Thus,
