RACK-1 expression and cytokine production in leukocytes, obtained from AD patients

Background and aims: The purpose of this study was to evaluate in vitro cytokine production in blood leukocytes obtained from sporadic AD patients, aged controls and young individuals. Methods: Diluted whole blood was treated in the presence or absence of LPS (1 mu g/mL) for varying times (3-48 h). The release of IL-8, IL-10 and TNF-alpha in conditioned media was evaluated by commercially available sandwich ELISA. Results: Data obtained are indicative of the presence of an unregulated systemic inflammation in AD patients. Leukocytes obtained from AD patients had increased spontaneous TNF-alpha. release and decreased LPS-induced IL-10 production, in comparison with both old controls and young subjects, while identical IL-8 production was observed in all groups. The lost finding indicates that there was no shift in the potency or efficacy of the response towards LPS with aging, but alterations in downstream signal transduction pathways are probably altered with aging and pathological conditions. Conclusions: The dysregulation of cytokine production observed in AD patients may partially be explained by a significant reduction in the expression of RACK-1, a protein crucial for integration of signaling pathways with different physiological functions, such as cytokine production.