Microglial responses to amyloid beta peptide opsonization and indomethacin treatment

• Published in: Journal of neuroinflammation 2005-08, Vol.2 (1), p.18-18, Article 18
• Main Authors: Strohmeyer, Ronald, Kovelowski, Carl J, Mastroeni, Diego, Leonard, Brian, Grover, Andrew, Rogers, Joseph
• Format: Article
• Language: English
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-2-18

Recent studies have suggested that passive or active immunization with anti-amyloid beta peptide (Abeta) antibodies may enhance microglial clearance of Abeta 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. We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Abeta deposits. Opsonization of the deposits with anti-Abeta IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Abeta, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-alpha 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 Abeta opsonization. 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 Abeta immunization, permitting unfettered clearance of Abeta while dampening secondary, inflammation-related adverse events.