Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients.
In an attempt to define potential immunological dysfunctions in schizophrenia, we determined the production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and soluble IL-2 receptor (sIL-2R) in a whole-blood assay after stimulation with phytohemagglutinin (PHA) as well as the serum concentrations of sIL-2R. Because CD4+CD45RO+T cells are the main producers of IFN-gamma, we determined the percentage of these cells, as well as of panT, CD4+T, and CD8+T cells, by flow cytometry. A whole-blood count was performed in addition. Two groups of patients were examined, paranoid-type and residual-type schizophrenics. The numbers of both monocytes and neutrophils, but not of lymphocytes, were increased significantly in the schizophrenic sample. The IFN-gamma production of the schizophrenics as a whole group, and of the paranoid patients, was reduced significantly in comparison with the control group (p < or = 0.05). The residual patients produced less IFN-gamma than the controls, but more than the paranoid patients. The latter differences did not reach statistical significance. The production of IL-4, which physiologically antagonizes the production of IFN-gamma, was not significantly higher in the patient group. No changes in the lymphocyte subpopulations were observed. The production of IL-2 showed a trend toward reduction in paranoid patients, but not in residual schizophrenics. The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls. In order to rule out a possible effect of cortisol on cytokine production, 20 schizophrenics were compared with 20 age- and gender-matched controls. However, neither elevated cortisol levels were detected in the schizophrenic sample, nor significant intercorrelations between cortisol levels and cytokine production, or levels of sIL-2R, respectively. In summary, our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect.
Wilke
I
I
Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Germany.
Arolt
V
V
Rothermundt
M
M
Weitzsch
C
C
Hornberg
M
M
Kirchner
H
H
D000328:Adult; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D012559:Schizophrenia / Q000097:blood* / Q000276:immunology*; D012563:Schizophrenia, Paranoid / Q000097:blood* / Q000276:immunology*
D016207:Cytokines; D007378:Interleukins; D007371:Interferon-gamma; D006854:Hydrocortisone