INVESTIGATIONS OF CYTOKINE PRODUCTION IN WHOLE-BLOOD CULTURES OF PARANOID AND RESIDUAL SCHIZOPHRENIC-PATIENTS

In an attempt to define potential immunological dysfunctions in schizo phrenia, we determined the production of interleukin-2 (IL-2), interle ukin-4, (IL-4), interferon-gamma (IFN-gamma), and soluble IL-2 recepto r (sIL-2R) in a whole-blood assay after stimulation with phytohemagglu tinin (PHA) as well as the serum concentrations of sIL-2R. Because CD( 4)(+)CD45RO(+)T cells are the main producers of IFN-gamma, we determin ed 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 ad dition. Two groups of patients were examined, paranoid-type and residu al-type schizophrenics. The numbers of both monocytes and neutrophils, but not of lymphocytes, were increased significantly in the schizophr enic sample. The IFN-gamma production of the schizophrenics as a whole group, and of the paranoid patients, was reduced significantly in com parison with the control group (p less than or equal to 0.05). The res idual patients produced less IFN-gamma than the controls, but more tha n the paranoid patients. The latter differences did not reach statisti cal significance. The production of IL-4, which physiologically antago nizes the production of IFN-gamma, was not significantly higher in the patient group. No changes in the lymphocyte subpopulations were obser ved. The production of IL-2 showed a trend toward reduction in paranoi d patients, but not in residual schizophrenics. The serum sIL-2R level s were elevated slightly in schizophrenics when compared with controls . In order to rule out a possible effect of cortisol on cytokine produ ction, 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 co rtisol levels and cytokine production, or levels of sIL-2R, respective ly. In summary, our data reinforce the possibility of immune dysfuncti on in schizophrenia and point to the possible relevance of disease sub groups in this respect.