Overproduction of IFN-γ and TNF-α from natural killer (NK) cells is associated with abnormal NK reactivity and cognitive derangement in Alzheimer's disease

S. B. Solerte, L. Cravello, E. Ferrari, M. Fioravanti

Research output: Contribution to journalArticle

Abstract

Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimer's type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN-γ and TNF-α (spontaneous and modulated by IL-2) from pure NK cells (CD 16+, CD 56+, CD 3-) were studied together with circulating IFN-γ and TNF-α levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher (p <0.001) IL-2 modulated NKCC (with IL-2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+35% and +99% from baseline) than in healthy subjects (+6% and +76% from baseline). Increased spontaneous and IL-2-induced release of IFN-γ and TNF-α from NK cells were found in DAT patients compared to healthy subjects (p <0.001), whereas no difference of serum IFN-γ and TNF-α was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN-γ and TNF-α from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK-derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.

Original languageEnglish
Pages (from-to)331-340
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume917
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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