Affiliations: [a] Department of Oncology and Neuroscience, University “G. d'Annunzio”, Chieti, Italy | [b] Catholic University, Rome, Italy | [c] Centre of Excellence on Aging, Chieti, Italy
Correspondence:
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Corresponding author: Marcella Reale, Department of Oncology and Neuroscience, Unit of Immunology, University “G. D'Annunzio”, N.P.D., Ed. C, III lev., Via dei Vestini, 31, 66123 Chieti, Italy. Tel./Fax: +39 871 3554029; E-mail: mreale@unich.it.
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Communicated by Alexandre de Mendonca.
Abstract: Cerebral inflammation as well as systemic immunological alterations has been reported in Alzheimer's disease (AD). We aimed to determine whether spontaneous and mitogen stimulated production of peripheral blood mononuclear cell (PBMC) cytokines, chemokines and chemokine receptors in clinically diagnosed patients with AD were unregulated. PBMC were purified from AD patients and from healthy controls. Supernatants were analyzed for cytokine levels by ELISA methods. mRNA expression was determined by RT-PCR. Expression of chemokine receptors CCR2 and CCR5 was determined by cytofluorimetric analysis. Both CCR5 and CCR2 expression were increased in AD patients respect to control subjects and the expression of CCR2 and CCR5 was more frequent on CD4+ and less frequent on CD8+ cells. Levels of Th1-type cytokine IFNγ and chemokine RANTES were increased and levels of Th2-type cytokine IL-4 and chemokine MCP-1 were reduced in AD patients compared with those of control subjects. Acetylcholinesterase inhibitor pyridostigmine bromide (AChEI)-therapy reduced CCR2, CCR5, RANTES and IFNγ expression and production in AD patients. CCR5, CCL5/RANTES, CCL2/MCP-1 and IFNγ expression and production were increased in PBMC treated with amyloid-β1–42. Addition of AChEI to PBMC suppresses CCL5/RANTES and IFNγ. The observed patterns of cyto-chemokine involvement strengthen the questions regarding the inflammatory theory in AD, and raise a pathophysiologic role for selective alteration of cyto-chemokine network.
