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. 2011 Jul 19;77(3):212-8.
doi: 10.1212/WNL.0b013e318225ae07. Epub 2011 Jul 13.

Proinflammatory cytokines, sickness behavior, and Alzheimer disease

C Holmes  1 , C Cunningham, E Zotova, D Culliford, V H Perry
Affiliations

Proinflammatory cytokines, sickness behavior, and Alzheimer disease

C Holmes et al. Neurology. .

Abstract

Background: In Alzheimer disease (AD), systemic inflammation is known to give rise to a delirium. However, systemic inflammation also gives rise to other centrally mediated symptoms in the absence of a delirium, a concept known as sickness behavior. Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior.

Objective: To determine if raised serum TNFα or IL-6 are associated with the presence of sickness behavior symptoms, independent of the development of delirium, in a prospective cohort study of subjects with AD.

Methods: A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers. Cognitive assessments, including assessments to detect the development of a delirium, and blood samples were repeated at 2, 4, and 6 months. The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2, 4, and 6 months.

Results: Raised serum TNFα and IL-6, but not CRP, were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior. These relationships are independent of the development of delirium.

Conclusions: Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior, which are common neuropsychiatric features found in AD. This association was independent of the presence of delirium.

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Figures

Figure 1
Figure 1. Frequency distribution of neuropsychiatric features in subjects with Alzheimer disease over the 6-month follow-up period by low or high levels of tumor necrosis factor–α (TNFα)
*p ≤ 0.05, ** p ≤ 0.01, adjusted for baseline age, gender, Alzheimer's Disease Assessment Scale Cognitive subscale score, and presence of delirium during follow-up.
Figure 2
Figure 2. Frequency distribution of neuropsychiatric features in subjects with Alzheimer disease over the 6-month follow-up period by low or high levels of interleukin-6 (IL-6)
*p ≤ 0.05, ** p ≤ 0.01, adjusted for baseline age and gender.
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References

    1. Kent S, Bluthe RM, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci 1992;13:24–28 - PubMed
    1. Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 2009;29:247–264 - PMC - PubMed
    1. Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988;12:123–137 - PubMed
    1. Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 2007;21:153–160 - PMC - PubMed
    1. Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci 2005;25:9275–9284 - PMC - PubMed