University of Illinois at Chicago, Department of Psychiatry, Chicago, IL 60612, USA.
University of Illinois at Chicago, Department of Psychiatry, Chicago, IL 60612, USA.
Schizophr Res. 2018 Feb;192:247-254. doi: 10.1016/j.schres.2017.04.043. Epub 2017 May 2.
Immune function abnormalities have been implicated in the pathophysiology of schizophrenia (SZ). This is primarily based on the observation that the levels of proinflammatory cytokines are significantly increased in the serum of SZ patients compared with normal control (NC) subjects. However, it is not known if similar cytokines abnormalities are also present in the brain of SZ patients. To further examine the involvement of inflammatory cytokines in the brain of SZ patients, we determined the protein and mRNA levels of TNF-α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, LTA and IL-1RA in the prefrontal cortex (PFC, Brodmann area 9) of SZ patients. We found that the protein and mRNA expression levels of the cytokines TNF-α and IL-6 are significantly increased and those of IL-10 are significantly decreased in the PFC of SZ patients. No difference in the protein and mRNA levels of IL-1β, IL-13, and IL-1RA was observed between SZ patients and NC subjects. The protein expression levels of IL-8 were significantly decreased and those of LTA were significantly increased in SZ patients, but no significant difference in the mRNA levels of IL-8 and LTA was observed between SZ patients and NC subjects. The levels of IL-2 were undetectable or very low in the postmortem brain of either SZ or NC subjects. These results suggest abnormalities of specific pro- and anti-inflammatory cytokines in the postmortem brain of SZ patients. These observations may have important implications in understanding the role of inflammatory cytokines in the pathophysiology of SZ.
免疫功能异常与精神分裂症（SZ）的病理生理学有关。这主要是基于这样的观察结果，即与正常对照（NC）受试者相比，SZ 患者的血清中促炎细胞因子水平显著升高。然而，SZ 患者的大脑中是否存在类似的细胞因子异常尚不清楚。为了进一步研究炎症细胞因子在 SZ 患者大脑中的参与情况，我们测定了 SZ 患者前额叶皮质（PFC，Brodmann 区 9）中 TNF-α、IL-1β、IL-2、IL-6、IL-8、IL-10、IL-13、LTA 和 IL-1RA 的蛋白和 mRNA 水平。我们发现，TNF-α和 IL-6 的蛋白和 mRNA 表达水平在 SZ 患者的 PFC 中显著升高，而 IL-10 的表达水平显著降低。SZ 患者和 NC 受试者之间，IL-1β、IL-13 和 IL-1RA 的蛋白和 mRNA 水平没有差异。IL-8 的蛋白表达水平在 SZ 患者中显著降低，而 LTA 的蛋白表达水平显著升高，但 SZ 患者和 NC 受试者之间，IL-8 和 LTA 的 mRNA 水平没有显著差异。IL-2 的水平在 SZ 或 NC 受试者的死后大脑中均无法检测到或非常低。这些结果表明 SZ 患者死后大脑中存在特定的促炎和抗炎细胞因子异常。这些观察结果可能对理解炎症细胞因子在 SZ 病理生理学中的作用具有重要意义。
