Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia on long-term treatment with antipsychotics

Abstract

The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced suppression of some inflammatory cytokines.

α4β2 Nicotinic Receptors Partially Mediate Anti-Inflammatory Effects through Janus Kinase 2-Signal Transducer and Activator of Transcription 3 but Not Calcium or cAMP Signaling

“…Nicotine exposure increased the expression of endoplasmic reticulum chaperones, down-regulated PICs, and induced up-regulation in h␣4␤2 SHEP1 cells (Hosur et al, 2009). Our findings point to a negative association between increases in ␣4␤2 receptor expression and down-regulation of PICs, which could account for the following: 1) loss of ␣4␤2 nAChRs observed in patients with neurological disorders, manifested by excess inflammation (Ripoll et al, 2004); in this case, PICs might be altering the assembly of nAChR subunits; and 2) although positron emission tomography and postmortem studies of the brains of long-term smokers reveal an appreciable increase in highaffinity binding sites for nicotine (Wü llner et al, 2008), longterm smokers with schizophrenia have lower inflammatory cytokines (IL-2 and IL-6) compared with their nonsmoking counterparts (Zhang et al, 2008). Therefore, the inverse correlation of smoking with development of neurological disorders might be due to a combination of the following: 1) nicotine up-regulates high-affinity ␣4␤2 receptors and their function, leading to cognitive and motor sensitization; and 2) nicotinic activation of ␣4␤2 and ␣7 receptors results in attenuation of anti-inflammatory responses (van der Zanden et al, 2009).…”

Smoking and Serum Lipid Profiles in Schizophrenia

“…Both antipsychotic medications and nicotine can decrease the activated immune response in patients with chronic schizophrenia [33,41]. For example, we have reported that IL-2 and IL-6 are significantly lower in chronic schizophrenic smokers than in non-smokers, and lower IL-2 levels are correlated with smoking more cigarettes [33]. It is likely that the alterations of the immune system in schizophrenic smokers are caused by the combined effects of antipsychotic medications and smoking.…”

“…Moreover, immune activation is particularly prominent in schizophrenic patients resistant to therapy [40,41]. Both antipsychotic medications and nicotine can decrease the activated immune response in patients with chronic schizophrenia [33,41]. For example, we have reported that IL-2 and IL-6 are significantly lower in chronic schizophrenic smokers than in non-smokers, and lower IL-2 levels are correlated with smoking more cigarettes [33].…”

“…For example, smoking decreases the levels of anti-inflammatory cytokines such as interleukin (IL)-10 and augments the production of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-a), and granulocyte-macrophage colony-stimulating factor [32]. Thus, the results suggested that smoking is an important contributor to the altered immune system in patients with chronic schizophrenia [33]. In addition, various abnormalities in the immune system are associated with schizophrenia [34][35][36][37].…”

Biomarkers and schizophrenia: a qualitative review

“…Multiple factors have been assigned potentially responsible for the discrepancy verified among studies, particularly when evaluating biomarkers (for example cytokines) in chronic SCZ patients on long-term antipsychotics. Patients' gender, age, body mass index (BMI), smoking and dietary habits, differences in measurement techniques, in tested material or in the stored period of the sample, sampling at different illness' stages (acute vs. chronic or active phase vs. remission), exposure to different type and dosage of antipsychotics, the length of treatment, the duration of hospitalisation, different clinical presentations, or the biological heterogeneity, were implicated in the aforementioned discrepancies [12,13]. Accordingly, an important characteristic that should be taken into account when investigating biomarkers in SCZ is the stage of the disease.…”