Altered Alterations of B Cell Activation in CSF of Schizophrenic 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.