Cargando…

Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease

BACKGROUND: Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural an...

Descripción completa

Detalles Bibliográficos
Autores principales: Puli, Lakshman, Pomeshchik, Yuriy, Olas, Katja, Malm, Tarja, Koistinaho, Jari, Tanila, Heikki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416679/
https://www.ncbi.nlm.nih.gov/pubmed/22642812
http://dx.doi.org/10.1186/1742-2094-9-105
_version_ 1782240421326356480
author Puli, Lakshman
Pomeshchik, Yuriy
Olas, Katja
Malm, Tarja
Koistinaho, Jari
Tanila, Heikki
author_facet Puli, Lakshman
Pomeshchik, Yuriy
Olas, Katja
Malm, Tarja
Koistinaho, Jari
Tanila, Heikki
author_sort Puli, Lakshman
collection PubMed
description BACKGROUND: Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer’s disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD. METHODS: We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy. RESULTS: We found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus. CONCLUSIONS: Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients.
format Online
Article
Text
id pubmed-3416679
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-34166792012-08-11 Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease Puli, Lakshman Pomeshchik, Yuriy Olas, Katja Malm, Tarja Koistinaho, Jari Tanila, Heikki J Neuroinflammation Research BACKGROUND: Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer’s disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD. METHODS: We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy. RESULTS: We found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus. CONCLUSIONS: Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients. BioMed Central 2012-05-29 /pmc/articles/PMC3416679/ /pubmed/22642812 http://dx.doi.org/10.1186/1742-2094-9-105 Text en Copyright ©2012 Puli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Puli, Lakshman
Pomeshchik, Yuriy
Olas, Katja
Malm, Tarja
Koistinaho, Jari
Tanila, Heikki
Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title_full Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title_fullStr Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title_full_unstemmed Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title_short Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease
title_sort effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416679/
https://www.ncbi.nlm.nih.gov/pubmed/22642812
http://dx.doi.org/10.1186/1742-2094-9-105
work_keys_str_mv AT pulilakshman effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease
AT pomeshchikyuriy effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease
AT olaskatja effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease
AT malmtarja effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease
AT koistinahojari effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease
AT tanilaheikki effectsofhumanintravenousimmunoglobulinonamyloidpathologyandneuroinflammationinamousemodelofalzheimersdisease