Patients with Alzheimer's disease display a pro-inflammatory phenotype

Interleukin-10 Production in Response to Amyloid-β Differs between Slow and Fast Decliners in Patients with Alzheimer’s Disease

“…Ex vivo, LPS-and A␤-induced IL-10 production by PBMCs of AD patients and age-matched controls. PBMCs (3.10 6 cells / ml) from AD patients (n = 30) and age-matched controls (n = 18) were cultured either in complete medium alone (open symbol), supplemented with 1 ng/ml of LPS (full symbol, A) during two days or supplemented with a pool of three A␤ peptides: 1 g/ml of fragment (1-16), 10 g/ml of fragment (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and 25 g/ml of fragment (1-40) (full symbol, B) during five days. Results have been showed as scatter plot and the median value is indicated by a black plain line.…”

“…However, some studies demonstrated a reduction of both pro-and antiinflammatory cytokines [30,31], suggesting a general impairment of immune functions in AD. Other studies demonstrated a decrease of IL-10 and an increase of pro-inflammatory cytokines IL-1␤, IL-6, and IFN-␥ [21,[32][33][34]. This variability could be explained by methodological differences among studies, including inclusion criteria of both AD patients and healthy controls and methods of mitogen-or A␤-stimulation.…”

“…Blood from all individuals was collected at the same time in the morning and employed for biochemical tests and PBMCs isolation. PBMCs were cultured in medium, medium+LPS (1 ng/ml), or medium+pool of three A␤ peptides: 1 g/ml of fragment (1-16), 10 g/ml of fragment (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and 25 g/ml of fragment (1-40) (Innovagen, Lund, Sweden). IL-10 production was measured with ELISA (Ready-SET-Go!…”

Increased production of inflammatory cytokines in mild cognitive impairment

“…Moreover, decreased production of the anti-inflammatory cytokine IL-10 in PBMCs stimulated with Aβ peptides was seen in AD (Arosio et al, 2004). However, other studies have shown elevated levels of TNF-α, IL-1β, IL-6, and IL-10 (Lombardi et al, 1999) and higher proto anti-inflammatory cytokine ratios, both IL-1β/IL-10 and IL-6/IL-10, released from LPS stimulated whole blood cultures from AD patients compared to controls, suggesting a proinflammatory phenotype in AD (Remarque et al, 2001). These seemingly contradictory reports may be partly explained by changes in inflammatory phenotype that are specific to certain disease stages as demonstrated by a study that found decreased production of IL-1β and IL-6 by stimulated blood cells in severe AD but not mild to moderate AD patients (Sala et al, 2003).…”

“…In general, PHA stimulates lymphocyte proliferation, while LPS stimulates monocytes to release IL-1 and TNF-α (Hsu and Wen, 2002;Tyrsted and Munch-Petersen, 1977;Zhu et al, 2000). Reports that demonstrate a difference in PBMC cytokine production between AD patients and controls have used different stimulants including PHA and LPS and various time points, including 24 and 48 hour incubations (Richartz et al, 2005;Remarque et al, 2001;Huberman et al, 1994). Because we designed this study as a comprehensive assessment of alterations in MCI subjects that have been previously reported in AD patients, both stimulants and time points were used.…”