Differential effects on T-cell function following exposure to serum from schizophrenia smokers

Abstract

Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effects of 'smoking-conditioned' serum obtained from schizophrenia and control subjects on healthy T cell in vitro. We found that T-cell proliferation was significantly increased following exposure to serum from smoking schizophrenia patients whereas no effect was observed when using serum from smoking control subjects or non-smoking patients and controls. We eliminated the possibility that these effects were due to quantitative differences in cigarette consumption as serum levels of the stable nicotine metabolite cotinine were similar in schizophrenic and control smokers. Molecular characterization showed that serum from patient smokers increased expression of T-cell activation markers CD69 high , CD25 high , co-stimulatory molecules CD26 þ , CD27 þ and CD28 þ , and decreased T-cell receptor complex components TCRa/b and CD3. Moreover, analysis of supernatants collected after T-cell exposure to serum from smoking patients showed a time-dependent decline in interleukin (IL)-2 levels, suggesting that the proliferation effect is promoted by enhanced IL-2 processing. These results suggest that cigarette smoking has selective effects on serum components that, in turn, lead to altered immune function in schizophrenia patients relative to healthy subjects. Further studies aimed at characterizing these components could result in a better understanding of the onset and aetiology of schizophrenia and potentially lead to novel therapeutic strategies.

Serum and gene expression profile of cytokines in first-episode psychosis

“…Cigarette smoking has been recently shown to have selective effects on serum components of patients with schizophrenia that lead to altered immune function different from healthy controls (Herberth et al, 2010). This might partly explain the specific effect of nicotine use on IL-6, and the lack of its effect on cytokine levels in our group of healthy controls.…”

Impaired glycolytic response in peripheral blood mononuclear cells of first-onset antipsychotic-naive schizophrenia patients

“…Unstimulated PBMCs from antipsychotictreated (AT) chronically ill schizophrenia patients were also investigated by LC-MS E to determine which markers may be normalized by treatment and which may be indicators of the underlying disease state. PBMCs were chosen as the tissue source in this study due to reports of immune dysfunction in schizophrenia patients 9,10 and as previous studies have shown that such cells are useful peripheral sources of biomarkers for studies of psychiatric illnesses. 11,12 In addition, numerous studies have shown that the brain and blood cells show a number of parallel responses, which suggest that the PBMCs may be a useful surrogate of brain function.…”

Do Defective Immune System-Mediated Myelination Processes Increase Postpartum Psychosis Risk?

“…The effects of antipsychotic administration on white matter integrity appear inconsistent and are more poorly defined, but there is some evidence for enhanced myelination via effects on oligodendrocytes 67 , 68 . Finally, rates of PP are higher in non-smokers than in smokers with bipolar disorder [69] ; this is interesting since smoking boosts numbers and/or function of Tregs in the large airways and lungs (and possibly other tissues) 70 , 71 and reduces Ccn3 expression in these tissues in a model system [72] .…”