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- Title
IL-10 and glucocorticoids inhibit Aβ(1–42)- and lipopolysaccharide-induced pro-inflammatory cytokine and chemokine induction in the central nervous system.
- Authors
Szczepanik, Ann Marie; Ringheim, Garth E.
- Abstract
Alzheimer's disease (AD) is characterized by neuropil threads composed of structurally abnormal neurites, neurons containing paired helical filaments of tau protein, and extracellular deposits of amyloid-β (Aβ) peptide, a protein fragment having neurotoxic and glial immune response activating potential. In the present study, we demonstrate that an acute intracerebroventricular (icv) injection of Aβ(1–42) in the mouse induces a time- and dose-dependent production of IL-1α, IL-1β, IL-6 and MCP-1 in the hippocampus and cortex as measured by ELISA. Cytokine and chemokine levels were maximal at 9 h, with MCP-1 and IL-1α remaining elevated over a 24 h period and IL-1β remaining elevated over a 48 h period. The temporal profile of Aβ-induced cytokine induction differed from that observed for LPS. Following an icv injection of LPS, maximal levels of IL-1α, IL-1β, IL-6 and MCP-1 were attained by 9 h and, except for MCP-1, returned to levels indistinguishable from control at 24 h. MCP-1 remained elevated at 24 h and returned to basal levels at 48 h. In contrast, little production of TNF-α was observed under either Aβ or LPS acute stimulus conditions. Treatment with anti-inflammatory agents such as prednisolone, dexamethasone, or IL-10 inhibited both Aβ- and LPS-induced cytokine and chemokine production in the brain. In summary, icv administration of Aβ and LPS induced elevated brain levels of pro-inflammatory cytokines that could be inhibited by immune suppressing drugs and anti-inflammatory proteins, thus providing support for the utility of anti-inflammatory therapeutics in modulating the immunopathology observed in brain inflammatory diseases such as AD.
- Subjects
INTERLEUKIN-10; GLUCOCORTICOIDS; ENDOTOXINS; CYTOKINES; CHEMOKINES
- Publication
Journal of Alzheimer's Disease, 2003, Vol 5, Issue 2, p105
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2003-5205