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., 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-1alpha, IL-8, IFNgamma, IL-1beta and TNFalpha 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-kappaBp65 levels and all studied cyto/chemokines and between NF-kappaBp65, 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.
Reale
M
M
Department of Oncology and Neuroscience, University G. D'Annunzio Chieti-Pescara, Italy. mreale@unich.it
Iarlori
C
C
Thomas
A
A
Gambi
D
D
Perfetti
B
B
Di Nicola
M
M
Onofrj
M
M
D000368:Aged; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D054405:Chemokine CCL3 / Q000097:blood / Q000235:genetics; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000235:genetics / Q000473:pathology*; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D011134:Polysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma