Background: Recent studies have suggested that passive or active immunization with anti-amyloid β peptide, (Aβ) antibodies may enhance microglial clearance of Aβ deposits from the brain, However, in a human clinical trial, several patients developed secondary inflammatory responses in brain that were sufficient to halt the study. Methods: We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Aβ deposits. Results: Opsonization of the deposits with and-Aβ IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Aβ, as well as exacerbated microglial secretion of the pro-Inflammatory cytokines TNF-α and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug (NSAID), had no effect on microglial chemotaxis or phagocytosis, but did significantly Inhibit the enhanced production of IL-6 after Aβ opsonization. Conclusion: These results are consistent with well known, differential NSAID actions on immune cell functions, and suggest that concurrent NSAID administration might serve as a useful adjunct to Aβ immunization, permitting unfettered clearance of Aβ while dampening secondary, Inflammation-related adverse events.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience