Article Abstract

C1Q/TNF-related protein 4 expression correlates with herpes simplex encephalitis progression

Authors: Wangshu Xu, Heng Zhou, Xiaojuan Li, Lu Wang, Xinwu Guo, Linlin Yin, Haoxiao Chang, Yuzhen Wei, Qingsong Li, Jinhai Deng, Xingang Zhou, Haifeng Yang, Xinghu Zhang, Fang Yi, Wenping Ma


Background: Herpes simplex encephalitis (HSE), an acute inflammatory disease of the central nervous system is caused by the herpes simplex virus infection. HSE occurs at any age, and it is often accompanied by high mortality and neurological dysfunction. The C1Q/TNF-related protein (CTRP) family, usually contains a homotrimeric structure, which comprises the N-terminal signal peptide and the C-terminal C1q globular domain. It has been demonstrated that CTRPs play pivotal roles in the inflammation process. CTRP4 is a member of the CTRP family and contains two C1q globular domains. Moreover, evidence shows that the recombinant human CTRP4 (rhCTRP4) protein exerts satisfactory anti-inflammatory effects in experimental colitis models via the NF-κB pathway. However, its role in inflammation-related neurological diseases remains unknown.
Methods: The purpose of this study is to evaluate the expression of CTRP4 and its correlation with HSE progression. We determined the serum CTRP4 levels in a normal brain, tuberculous meningitis (TBM), bacterial meningitis (BM) and HSE.
Results: We found that compared to a normal brain, TBM and BM, CTRP4 was significantly increased in HSE. Moreover, in the course of HSE, serum interleukin (IL-6) and necrosis factor-α (TNF-α) were also increased and were closely associated with CTRP4 expression. CTRP4 expression was examined by immunohistochemistry (IHC) in the normal control brain tissues, HSE, TBM and BM brain tissues. High positively expression of CTRP4 was found in HSE. In the normal brain tissue, TBM, and BM brain tissues, CTRP4 showed a weak expression. In the clinical evaluation, CTRP4 expression correlated closely with an ascending stage of the disease [mini-mental state examination (MMSE) evaluation, MRI imaging).
Conclusions: Our findings suggest that CTRP4 is highly expressed in HSE and is closely related to the progression of HSE. Thus, CTRP4 may serve as a potential severity index for HSE and targeting CTRP4 might be a promising therapeutic strategy against HSE.