CSF Cytokines in Aging, Multiple Sclerosis, and Dementia
Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We c...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00480/full |
| _version_ | 1811298654695194624 |
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| author | William T. Hu William T. Hu Jennifer Christina Howell Jennifer Christina Howell Tugba Ozturk Umesh Gangishetti Alexander L. Kollhoff Jaime M. Hatcher-Martin Albert M. Anderson William R. Tyor William R. Tyor |
| author_facet | William T. Hu William T. Hu Jennifer Christina Howell Jennifer Christina Howell Tugba Ozturk Umesh Gangishetti Alexander L. Kollhoff Jaime M. Hatcher-Martin Albert M. Anderson William R. Tyor William R. Tyor |
| author_sort | William T. Hu |
| collection | DOAJ |
| description | Inflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23–86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon–gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. We further found greater age-related increases in TNF-α, IL-10, and IL-8 relative to increases in IP-10 levels, consistent with a shift from Th1 to other inflammatory phenotypes. Finally, when we analyzed the same four cytokines in people with neurological disorders, we found that MS and AD, but not PD or dementia with Lewy bodies, further accentuated the age-related shift from Th1- to non-Th1-related cytokines. We propose that CSF cytokine levels represent powerful surrogates of brain inflammation and aging, and some, but not all, neurological disorders accelerate the shift away from Th1 phenotypes. |
| first_indexed | 2024-04-13T06:23:32Z |
| format | Article |
| id | doaj.art-546ac5ea5dc541218269c0a68915eb60 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T06:23:32Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-546ac5ea5dc541218269c0a68915eb602022-12-22T02:58:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00480430741CSF Cytokines in Aging, Multiple Sclerosis, and DementiaWilliam T. Hu0William T. Hu1Jennifer Christina Howell2Jennifer Christina Howell3Tugba Ozturk4Umesh Gangishetti5Alexander L. Kollhoff6Jaime M. Hatcher-Martin7Albert M. Anderson8William R. Tyor9William R. Tyor10Department of Neurology, Emory University, Atlanta, GA, United StatesCenter for Neurodegenerative Disease, Emory University, Atlanta, GA, United StatesDepartment of Neurology, Emory University, Atlanta, GA, United StatesAlzheimer's Disease Research Center, Emory University, Atlanta, GA, United StatesDepartment of Neurology, Emory University, Atlanta, GA, United StatesDepartment of Neurology, Emory University, Atlanta, GA, United StatesDepartment of Neurology, Emory University, Atlanta, GA, United StatesJean and Paul Amos Parkinson's Disease and Movement Disorders Program, Emory University, Atlanta, GA, United StatesDepartment of Internal Medicine, Emory University, Atlanta, GA, United StatesDepartment of Neurology, Emory University, Atlanta, GA, United StatesAtlanta VA Medical Center, Decatur, GA, United StatesInflammation is a common process involved in aging, multiple sclerosis (MS), and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), but there is limited evidence for the effects of aging on inflammation in the central nervous system. We collected cerebrospinal fluid (CSF) from 105 healthy control subjects representing a wide age range (23–86), and analyzed levels of cytokines associated innate immunity (TNF-α) and different T-helper subtypes: interferon–gamma induced protein 10 (IP-10) for Th1, interleukin-10 (IL-10) for Th2, and interleukin 8 (IL-8/CXCL8) for Th17. We show that CSF levels of TNF-α, IP-10, and IL-8 all increased linearly with age, but levels of IL-10 demonstrated a U-shaped relationship with age. We further found greater age-related increases in TNF-α, IL-10, and IL-8 relative to increases in IP-10 levels, consistent with a shift from Th1 to other inflammatory phenotypes. Finally, when we analyzed the same four cytokines in people with neurological disorders, we found that MS and AD, but not PD or dementia with Lewy bodies, further accentuated the age-related shift from Th1- to non-Th1-related cytokines. We propose that CSF cytokine levels represent powerful surrogates of brain inflammation and aging, and some, but not all, neurological disorders accelerate the shift away from Th1 phenotypes.https://www.frontiersin.org/article/10.3389/fimmu.2019.00480/fullinflammagingneuroinflammation and neurodegenerationIP10IL10IL8Alzheimer's disease |
| spellingShingle | William T. Hu William T. Hu Jennifer Christina Howell Jennifer Christina Howell Tugba Ozturk Umesh Gangishetti Alexander L. Kollhoff Jaime M. Hatcher-Martin Albert M. Anderson William R. Tyor William R. Tyor CSF Cytokines in Aging, Multiple Sclerosis, and Dementia Frontiers in Immunology inflammaging neuroinflammation and neurodegeneration IP10 IL10 IL8 Alzheimer's disease |
| title | CSF Cytokines in Aging, Multiple Sclerosis, and Dementia |
| title_full | CSF Cytokines in Aging, Multiple Sclerosis, and Dementia |
| title_fullStr | CSF Cytokines in Aging, Multiple Sclerosis, and Dementia |
| title_full_unstemmed | CSF Cytokines in Aging, Multiple Sclerosis, and Dementia |
| title_short | CSF Cytokines in Aging, Multiple Sclerosis, and Dementia |
| title_sort | csf cytokines in aging multiple sclerosis and dementia |
| topic | inflammaging neuroinflammation and neurodegeneration IP10 IL10 IL8 Alzheimer's disease |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00480/full |
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