Enhancement of immune response by phenothiazine administration in vivo

The natural killer (NK) cell activity and PHA-induced mitogenesis of the peripheral blood mononuclear cells (PBMC) were assessed in a group of schizophrenic patients treated with phenothiazines and haloperidol for different lengths of time. Significantly higher levels of NK cytotoxicity and lymphocyte mitogenesis were observed in the patients as compared to those in age and sex-matched healthy volunteers. Enhancement of NK activity in the patients depended on the duration and continuity of treatment with these calmodulin antagonists. Increased susceptibility to chlorpromazine (CPZ, a phenothiazine derivative)-induced in vitro inhibition of basal and mitogen stimulated tritiated thymidine incorporation was observed in the patients' lymphocytes, though the reversibility of CPZ binding was similar in these cells and in normal PBMC. The data suggested that continuous in vivo exposure to phenothiazines and haloperidol resulted in stimulation of lymphocyte activity. The enhanced lymphocyte activity following treatment with calmodulin antagonists may be associated with the antineoplastic activity of these drugs.