Peripheral cytokines profile in Parkinson's Disease

Higher levels of proinflammatory cytokines are found in Parkinson’s disease (PD) patient’s brains and inflammation is thought to be a major contributor to the neurodegeneration. During the inflammatory process, microglial release of proinflammatory cytokines act on the endothelium of blood–brain barrier (BBB) cells to stimulate upregulation of adhesion molecules. Consequently, this upregulation leads to the recruitment of passing T cells and monocytes, which express the counter receptors, that then go on to release more cytokines [Whitton, P.S., 2007. Inflammation as a causative factor in the aetiology of Parkinson’s disease, Br. J. Pharmacol. 50, 963–976; Kortekaas, R., Leenders, K.L., Van Oostrom, J.C., Vaal- burg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H., 2005. Blood–brain barrier dysfunction in parkinsonian midbrain in vivo, Ann. Neurol. 57, 176–179]. In addition, a systemic inflammatory response results in the production of cytokines which circulate in the blood and communicate with neurons within the brain. Thus, a central inflammatory reaction interacts with peripheral blood mononuclear cells (PBMCs) mod- ulating immune activity. The present study investigates levels of production and expression of cyto/che- mokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1a, IL-8, IFNc, IL-1b and TNFa were significantly higher in PD patients than in HC subjects (p < 0.001), as determined by RT-PCR and Elisa methods. Cyto/ chemokine levels were significantly correlated with UPDRS III and H/Y stage (p < 0.001). The Pearson’s correlation coefficient (R) was also used to assess the strength of the relationship between NF-jBp65 lev- els and all studied cyto/chemokines and between NF-jBp65, UPDRS III and H/Y score in PD patients. The overall results strengthen work associated with PD. and extend the knowledge of the peripheral dysregulation in the cytokine net-