This phenomenon is associated with the covalent bonding between neutrophils and a reactive nitrenium ion, the oxidized form of olanzapine. less studied alterations also have a significant impact in the patient’s health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders. (1.5C7.5 g/mL) inhibits Th1 differentiation by preventing the expression of transcription factor T-bet but not that of STAT-4 in T DDPAC cells; clozapine also inhibited Th1 differentiation by blocking the AKT activation pathway (88). Moreover, clozapine (20 M) promoted the differentiation of Treg cells and the expression of Foxp3 in splenocytes and lymph node cells from C57BL6/J mice in a model of experimental autoimmune encephalomyelitis (EAE) (15). Regarding the effects of clozapine in MQs it has been described that clozapine increased IL-10 production and decreased IL-12 secretion in MQs after 5 days of incubation and when it is stimulated with lipopolysaccharide (LPS) for 24 h (89). Similarly, clozapine (10C100 M) reduced nitric oxide (NO) and IL-12p40 Salinomycin (Procoxacin) production by LPS-stimulated bone marrow-derived macrophages (BMDM) from female C57BL/6 mice (90). In studies carried out in animal models, similar effects to those described above in cell cultures have been observed in MQs. In a perinatal phencyclidine rat model, the administration of clozapine increased IL-6 and TNF- with sex-specific changes (91), which can fit in the theory of cytokine signature observed in blood leukocytes from healthy volunteers incubated with clozapine (1 M) (92). It has also been reported that, in Wistar rats, clozapine (45 mg/kg/day) induced myocarditis related with lymphocytic infiltrates, which induced the release of reactive oxygen species (ROS), cytokines, and TNF- (93). Additionally, a perinatal model of 90 day-old Wistar rats prenatally treated with LPS reported that daily clozapine (10 mg/kg) significantly Salinomycin (Procoxacin) reduced IL-1, TNF-, and IL-2 levels (60, 94). Finally, consideration should be given to the changes in the profile of circulating cytokines induced by clozapine consumption. For instance, nine patients with diagnosed schizophrenia or schizoaffective disorder, who were treated with clozapine 100C400 mg/day, showed increased risk of developing fever after the first intake, and IL-6 might play a specific role in the interaction effect between treatment duration and fever development (94, 95). Clozapine has also been shown to increase soluble IL-2 receptor (sIL-2R) and IL-6 levels (96, 97). Similarly, the adipokine resistin was associated with several acute and chronic inflammatory states and promoted the expression of TNF- and IL-6 by human Salinomycin (Procoxacin) mononuclear cells (97) (see Table 2). Table 2 Immunoendocrine peripheral effects induced by atypical antipsychotics. gene (0.25C6 mg/day, 0.1C143 months) (131). In addition, HPRL during treatment with risperidone/paliperidone in schizophrenic patients showed an association with rs40184 and rs3863145 variants in gene of blood leukocyte DNA (132). All the studies that showed elevated PRL levels in the pediatric population are in accordance with a meta-analysis that presented a relation between risperidone treatment and high PRL (130). The possible mechanism by which risperidone causes HPRL is associated with the transcriptional upregulation of neuropeptide Y (NPY) secreted by the arcuate hypothalamic nucleus due to the high affinity of risperidone to 5-HT2A receptors. NPY inhibits tyrosine hydroxylase expression in the paraventricular nucleus and thus reduces DA synthesis, which in turn would diminish the inhibition of PRL expression induced by DA. The reduction in DA would cause the overexpression of PRL in the pituitary and ultimately induce HPRL (133). Studies have shown that, in addition to PRL increase, other hormone profiles such.