title: The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders.
abstract: Mental health disorders(MHD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been widely studied. However, the underlying role of inflammatory cytokines and their associated signaling pathways have not been investigated. Here, we report the potential role of cytokines and associated signaling pathways in CP/CPPS patients with MHD and in a CP/CPPS animal model. CP/CPPS patients (n = 810) and control subjects (n = 992) were enrolled in this case-control multicenter study, and serum cytokine levels were measured. Male Sprague-Dawley rats received multiple intracutaneous injections of an immuno-agent along with a pertussis-diphtheria-tetanus triple vaccine for autoimmune CP/CPPS development. The results revealed that, in CP/CPPS patients with significant MHD, elevated IL-1α, IL-1β, IL-4, IL-13, and TNF-α serum levels were observed. The above five cytokines in CP/CPPS rats were significantly elevated in prostate tissue (p < 0.05), and IL-1β levels were elevated in serum and cerebrospinal fluid. In behavioral tests, CP/CPPS rats showed anxiety- and depression-like symptoms, and impaired spatial and associative memory performance (p < 0.05). In the CP/CPPS group, ERK1/2 phosphorylation levels were increased in the amygdala and nucleus accumbens, and decreased in the hippocampus, but not caudate nucleus. Thus, prostate-derived cytokines, especially IL-1β, cross the blood brain barrier and may lead to enhanced ERK1/2 signaling in several brain areas, possibly underlying induction of CP/CPPS-related MHD.
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, P. R. China.|Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Hualan
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University &Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, P. R. China.
authors.forename: Yinying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, P. R. China.
authors.forename: Yehao
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University &Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, P. R. China.
authors.forename: Jiefeng
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, 200032, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Urology, University of California, San Francisco, CA, 94143, USA.
authors.forename: Ching-Shwun
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, P. R. China.
authors.forename: Jican
authors.initials: J
authors.lastname: Dai
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002908:Chronic Disease; D059350:Chronic Pain / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008603:Mental Health; D017699:Pelvic Pain / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011467:Prostate / Q000378:metabolism; D011472:Prostatitis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4