SHORT AND LONG-TERM IMMUNOSUPPRESSIVE EFFECTS OF CLOZAPINE AND HALOPERIDOL

In line with the autoimmune hypothesis of schizophrenia we have tested in this study whether the commonly used neuroleptics, clozapine and h aloperidol can also act as systemic immunosuppressants, Twenty one hos pitalized chronic schizophrenic patients participated in the study. Fi ve were free of neuroleptic treatment while the other 16 were under ch ronic treatment with either clozapine (n = 8), or haloperidol(n = 8). Fourteen age matched normal subjects served as the control group. Conv entional in vitro mitogenic stimulation of peripheral blood lymphocyte s with phytohaemagglutinin (PHA) indicated a clear suppression of resp onsiveness of approximately 50% in all treated patients. The PHA respo nse of the untreated patients was virtually identical to that of the c ontrol group. The in vitro effect of haloperidol and clozapine on PHA stimulation of lymphocytes from normal subjects was determined by H-3- thymidine uptake and secretion of interleukin-2, interleukin-4 and int erferon-gamma. Both clozapine and haloperidol suppressed thymidine inc orporation and cytokine secretion at a drug concentration of above 1 m u M, reaching full suppression at 50 mu M. Similar suppressive effects of clozapine and haloperidol were also observed in mixed lymphocyte r eaction of mouse lymphocytes. Assays with radioactive ligands indicate d that clozapine is not incorporated into the lymphocytes but presumab ly exerts its action by binding to specific surface sites, The long te rm immune suppression induced by neuroleptic treatment may inhibit put ative autoimmune responses against neurological sites and could thus a ct synergistically with the direct antagonistic action on brain recept ors for the overt amelioration of psychotic behaviour. (C) 1997 Elsevi er Science B.V.