4.7 Article

Peripheral cytokines profile in Parkinson's disease

Journal

BRAIN BEHAVIOR AND IMMUNITY
Volume 23, Issue 1, Pages 55-63

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2008.07.003

Keywords

Cyto/chemokines; NF-kappa B; Parkinson's disease; PBMC

Funding

  1. Italian MIUR

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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., Vaalburg, 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) modulating immune activity. The present study investigates levels of production and expression of cyto/chemokines by PBMCs in PD patients. Basal and LPS-induced levels of MCP-1, RANTES, MIP-1 alpha, IL-8, IFN gamma, IL-1 beta and TNF alpha 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-kappa Bp65 levels and all studied cyto/chemokines and between NF-kappa Bp65, UPDRS III and H/Y score in PD patients. The overall results strengthen and extend the knowledge of the peripheral dysregulation in the cytokine network associated with PD. (c) 2008 Elsevier Inc. All rights reserved.

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