Serum cytokine level and production of reactive oxygen species (ROS) by blood neutrophils from a schizophrenic patient with hypersensitivity to neuroleptics.

Background: There have been few publications concerning the role of the immune system in neuroleptic intolerance. Some studies have shown that in neuroleptic malignant syndrome (NMS), associated with disseminated intravascular coagulation (DIC), the serum level of tumor necrosis factor alpha (TNF-alpha) increases significantly, which is thought to trigger the onset of DIC.

Case Report: A 23-year-old woman suffering from catatonic schizophrenia developed hypersensitivity to neuroleptics. One month before being referred to the present authors, she had a haloperidol-induced NMS episode in another psychiatric hospital, with high temperature, CPK activity, muscle rigidity and leukocytosis. On admission to our clinic and after treatment with promazine, laboratory tests showed an increase in serum CPK activity and mild leukocytosis. Neuroleptic treatment was discontinued, and the serum level of CPK and white blood cell count was monitored daily for 7 days, as well as the serum level of some cytokines and the production of reactive oxygen species (ROS) by blood neutrophils. The serum levels of interleukin 1 alpha (IL-1), IL-6 and TNF-alpha changed significantly over the observation period, forming waves with peak activity of IL-6 and TNF-alpha exceeding normal levels. The level of IL-1 alpha was within the control range. ROS production by the patient's blood neutrophils was also increased, as well as catalase serum activity.

Conclusions: Some proinflammatory cytokines may participate in the mechanisms leading to the development of neuroleptic intolerance in schizophrenic patients. Cytokine-stimulated ROS production may participate in tissue injury and increase CPK serum activity.