ALTERED
REGULATION OF B CELL ACTIVATION IN CSF OF SCHIZOPHRNIC PATIENTS
Markus J.
Schwarz*, Michael Riedel, Norbert Müller, Manfred Ackenheil.
Psychiatric Hospital, University of Munich, Munich, Germany
An altered antibody production in
schizophrenic patients as been described in a considerable number
of publications. Though the results are inconsistent regarding
the antigen specificity, the majority of authors described higher
amounts of antibodies in schizophrenic patients than in control
subjects. In vitro studies using stimulated lymphocytes showed a
reduced production of Interferon-g (IFN-g ) in
patients with schizophrenia, indicating a reduced activity of
cellular immune functions. These results indicate a shift from
cellular to humoral immune reactivity in schizophrenia.
The aim of our study was to
evaluate a parameter for antibody production independent from
antigen- or tissue-specificity especially in cerebrospinal fluid
(CSF) of schizophrenic patients. We focused on Interleukin-6
(IL-6) and its receptor, which play a central role in B cell
activation and antibody production. The IL-6 receptor complex is
composed of the IL-6 receptor (IL-6R, a chain) and
the signal transducing subunit gp130 (b chain). Both
subunits appear as measurable soluble forms in serum and CF
(sIL-6R and sgp130).
We investigated CSF
concentrations of IL-6, sIL-6R and spg130 in 51 schizophrenic
patients, 22 depressive patients and 22 healthy individuals.
Mean concentrations of IL-6
showed no differences between the three groups. However, the
concentrations of sIL-6R were decreased in CSF of schizophrenic
(884.5± 249.6 ng/ml) and of depressed patients (1003±
376.7 ng/ml), compared to the healthy individuals (1232.7±
410.4 ng/ml) (ANOVA: p=.015). The concentrations of sgp130 in CSF
of schizophrenic patients (36.4± 10.9 ng/ml)
were highly significant decreased compared to depressed patients
(46.6± 10.1 ng/ml) and healthy controls (45.1±
12.7 ng/ml) (ANOVA:p=.001). Determination of these parameters in
serum, which had been carried out in parallel, showed no
differences in any of the parameters.
Our results strongly indicate an
altered regulation of both IL-6 receptor subunits in
schizophrenic patients, especially a decrease of the soluble
gp130. This altered regulation seems to be limited to the
intrathecal compartment. The important role of the IL-6 system in
B cell activation and the inhibiting role of the soluble form of
gp130 points to an disturbance in the regulation of the humoral
immune system which might further result in increased antibody
production. The reason and the pathophysiological relevance of
these findings remain to be clarified. A relationship to an
additional role of IL-6, the neurotrophic property, could be
taken into account.