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ABSTRACT: MCP-1 and RANTES are molecules that regulate monocyte and T-lymphocyte recruitment towards sites of inflammation. We sought to evaluate the role of these chemokines in Alzheimer's disease (AD), and the effect of acetylcholinesterase inhibitor (AchEI) therapy on their release from peripheral blood mononuclear cells (PBMC). MCP-1 and RANTES mRNA expressions were determined by RT-PCR and the amount of secreted chemokines was assayed using specific ELISA methods from purified PBMC from each AD patients (n = 40) at the time of enrolment (T0) and after 1 month of treatment with AchEI (T1) and from 20 healthy age and sex-matched subjects (HC). We found that expression and production of MCP-1 in AD patients was significantly lower than in HC subjects. After 1 month of therapy with AchEI (Donepezil), MCP-1 levels increased in each patient. However, higher levels were detected for RANTES in AD patients compared to control subjects and in AD patients treated with Donepezil. MCP-1 and RANTES have a compensatory role in balancing the impaired mechanisms involved in immune response during ageing. Our present findings suggest that these two chemokines are both involved in AD pathogenesis and might reflect different states of activation and/or responsiveness of PBMC from AD patients, contributing to the impaired of the peripheral immune system in these patients.
Experimental Gerontology 08/2005; 40(7):605-11. · 3.74 Impact Factor
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ABSTRACT: Many factors are involved in the pathogenesis of Alzheimer's disease (AD), and inflammatory-immunologic activation seems to play a major role. One strategy for treatment of AD has been to use acetylcholinesterase (AChE) inhibitors to increase the levels of acetylcholine and enhancing cholinergic activity in the affected regions of the brain. Cholinergic compounds modulate the immune system, therefore secretion, by peripheral blood mononuclear cells (PBMC), of cytokines was investigated in age-matched controls and in AD patients. Cytokines released by PBMC from AD patients enrolled as pre-treatment patients (T0) and as post-treatment with AchEI (T1), were detected by ELISA assay. The result showed an increase in oncostatin M, interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) secretion in AD patients compared to healthy controls, and a decrease of cytokine levels in each AD patients treated for 1 month with an acetylcholinesterase inhibitor (AchEI). In conclusion, the results of this study show that the complex pathology in AD may be reflected in a pattern of altered cytokine secretion from PBMC.
Experimental Gerontology 04/2005; 40(3):165-71. · 3.74 Impact Factor
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Francesco Gambi,
Marcella Reale,
Carla Iarlori,
Anatolia Salone,
Lucia Toma,
Carlo Paladini,
Giovanna De Luca,
Claudio Feliciani, Mirella Salvatore,
Rosa M. Salerno,
Theoharis C. Theoharides,
Pio Conti,
Michael Exton,
Domenico Gambi
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ABSTRACT: The study evaluates the expression and production of cytokines in peripheral blood mononuclear cells of patients with Alzheimer disease treated or not treated with acetylcholinesterase inhibitor, which enhances neuronal transmission. Cytokines associated with brain inflammation such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α have been implicated in the regulation of amyloid peptide protein synthesis. The anti-inflammatory cytokine, IL-4, may suppress the activity of IL-1β.
Patients were assessed for clinical and immunologic features at baseline and after 1 month of treatment with Donepezil, an acetylcholinesterase inhibitor. Peripheral blood mononuclear cells were cultured with and without phytohemagglutinin stimulation. IL-1β and IL-4 levels were measured by enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to determine the expression of cytokines in peripheral mononuclear cells. Compared with untreated patients and healthy control subjects, IL-1β levels and expression decreased in Alzheimer disease patients treated with Donepezil (P < 0.001). In contrast, IL-4 levels and expression were significantly higher in Alzheimer patients treated with the acetylcholinesterase inhibitor. This increment was observed in both unstimulated and phytohemagglutinin-stimulated peripheral blood mononuclear cells.
Journal of Clinical Psychopharmacology 05/2004; 24(3):314-321. · 4.10 Impact Factor
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ABSTRACT: Elevated levels of cytokines have been detected in brains of Alzheimer's disease (AD) patients, and altered peripheral levels of IL-1beta, TNFalpha and IL-6 have been reported in these patients. We studied the ability of PBMC from patients with AD, matched with a control group, to release pro- and anti-inflammatory cytokines, and the effect of AChEI treatment on cytokine release. Our data indicates that AChEI treatment down-regulates IL-1, IL-6 and TNF, and up-regulates the expression and production of IL-4 in PBMC in AD patients, and that AChEI leads to the remodelling of the cytokine network, probably acting on the lymphocytic cholinergic system.
Journal of Neuroimmunology 04/2004; 148(1-2):162-71. · 2.96 Impact Factor
