Dexamethasone inhibits TNF-alpha synthesis more effectively in Alzheimer's disease patients than in healthy individuals.
Inflammatory mechanisms are involved in the pathogenesis of Alzheimer's disease (AD). It is postulated that cytokine synthesis is altered in AD patients compared with nondemented subjects. Glucocorticoids play an important role in cytokine synthesis. We assessed the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) and interleukin-12 (IL-12) and its regulation by dexamethasone in AD patients in vitro. Cytokine levels were measured using the ELISA method in unstimulated, LPS-stimulated or whole-blood samples incubated with LPS and dexamethasone from 18 AD patients and 12 controls. The cytokine levels spontaneously produced by blood cells after incubation with LPS or LPS and dexamethasone did not differ significantly between groups. Dexamathasone inhibited TNF-alpha synthesis by LPS-stimulated blood cells more effectively in AD patients than in controls. These results suggest that cytokine synthesis in AD patients could be regulated by glucocorticoids in a different way than in nondemented subjects.
D000544:Alzheimer Disease / Q000378:metabolism*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone