Microglial responses to amyloid β peptide opsonization and indomethacin treatment

Ronald Strohmeyer, Carl J. Kovelowski, Diego Mastroeni, Brian Leonard, Andrew Grover, Joseph Rogers

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number18
JournalJournal of Neuroinflammation
Volume2
DOIs
StatePublished - Aug 19 2005
Externally publishedYes

Fingerprint

Amyloid
Indomethacin
Anti-Inflammatory Agents
Chemotaxis
Phagocytosis
Peptides
Interleukin-6
Pharmaceutical Preparations
Passive Immunization
Brain
Microglia
Autopsy
Immunization
Alzheimer Disease
Vaccination
Therapeutics
Immunoglobulin G
Clinical Trials
Cytokines
Inflammation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Microglial responses to amyloid β peptide opsonization and indomethacin treatment. / Strohmeyer, Ronald; Kovelowski, Carl J.; Mastroeni, Diego; Leonard, Brian; Grover, Andrew; Rogers, Joseph.

In: Journal of Neuroinflammation, Vol. 2, 18, 19.08.2005.

Research output: Contribution to journalArticle

Strohmeyer, Ronald ; Kovelowski, Carl J. ; Mastroeni, Diego ; Leonard, Brian ; Grover, Andrew ; Rogers, Joseph. / Microglial responses to amyloid β peptide opsonization and indomethacin treatment. In: Journal of Neuroinflammation. 2005 ; Vol. 2.
@article{4bce4d0f95d548139b44dd10031e88b5,
title = "Microglial responses to amyloid β peptide opsonization and indomethacin treatment",
abstract = "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.",
author = "Ronald Strohmeyer and Kovelowski, {Carl J.} and Diego Mastroeni and Brian Leonard and Andrew Grover and Joseph Rogers",
year = "2005",
month = "8",
day = "19",
doi = "10.1186/1742-2094-2-18",
language = "English (US)",
volume = "2",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Microglial responses to amyloid β peptide opsonization and indomethacin treatment

AU - Strohmeyer, Ronald

AU - Kovelowski, Carl J.

AU - Mastroeni, Diego

AU - Leonard, Brian

AU - Grover, Andrew

AU - Rogers, Joseph

PY - 2005/8/19

Y1 - 2005/8/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27344447969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27344447969&partnerID=8YFLogxK

U2 - 10.1186/1742-2094-2-18

DO - 10.1186/1742-2094-2-18

M3 - Article

AN - SCOPUS:27344447969

VL - 2

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

M1 - 18

ER -