Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer's disease

A growing body of evidence points out the potential role of inflammatory me chanisms in the pathophysiology of brain damage in dementia. In previous st udies, we have demonstrated intrathecal production of the proinflammatory c ytokine tumor necrosis factor (TNF)alpha in patients with Alzheimer's disea se (AD). The aim of the present study was to investigate the downstream pro ducts of TNF-alpha expression including interleukin (1L)1 beta and its natu rally occurring antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels were related to neuronal damage, as measured by intrath ecal tau and beta -amyloid concentration and certain clinical features of t he disease. Fifty-two patients with AD and 25 healthy controls were analyze d with respect to cerebrospinal fluid (CSF) levels of IL-1 beta and IL-1ra. CSF IL-1 beta was neither detectable in CSF of AD nor in control CSF. In c ontrast, a significantly lower (p < 0.01) number of patients (24 of 49) tha n of controls (20 of 24) showed detectable levels of IL-1 ra in the CSF. Th e intrathecal levels of IL-1 ra were significantly lower in patients with A D than in the controls. Our study demonstrates a decreased production of th e anti-inflammatory compound IL-1ra, suggesting a propensity towards inflam mation in patients with AD. Copyright <(c)> 2001 S. Karger AG, Basel.