Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans

Systemic TNF-α produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration

“…The evidence that these effects are robust in normal healthy humans remains relatively limited despite multiple rodent studies suggesting such deficits (Cunningham and Sanderson, 2008, Yirmiya and Goshen, 2011, Czerniawski and Guzowski, 2014). Though some effects have been observed in humans these have been relatively mild or inconsistent (Reichenberg et al, 2001, Grigoleit et al, 2010) or noted on tasks that are relatively difficult (Harrison et al, 2014). The evidence that systemic inflammation has more robust effects on the frail or degenerating brain is accumulating in rodent studies (Barrientos et al, 2006, Buchanan et al, 2008, Field et al, 2012, Murray et al, 2012) and this is consistent with inflammatory triggering of human disorders such as delirium, which is a profound and acute cognitive impairment that frequently occurs during acute medical illness or after inflammatory traumas such as orthopedic fracture and surgery (Cunningham and Maclullich, 2013, Inouye et al, 2014).…”

Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans

“…Studies in experimental animals together with clinical observations in humans suggest a cytokine-mediated modulation of memory functions as a consequence of acute peripheral inflammatory processes [3], [37]. However, data in humans so far reported inconsistent results of experimental endotoxemia with a significant improvement [24] or no effect on working memory [25], [27]. These conflicting results might be either due to the different experimentally induced grades of inflammation or the neuropsychological tools (Digit Span Forward, Backward Test by Wechsler) employed in these studies to assess working memory performance.…”

“…Studies in experimental animals demonstrated that systemic immune activation by viral, bacterial, or parasitic infections result in impaired memory functioning [18], [19], [20], [21], [22], [23]. Experimental approaches in humans, employing lipopolysaccharide (LPS)-induced immune activation to investigate the effects of a peripheral inflammatory response on learning and memory reported either increased [24], no [25], [26], [27] or decreased [28] cognitive performance after LPS administration. Reasons for these discrepancy might be the different quality and concentrations of LPS administered together with distinct time intervals of testing memory performance and the different memory processes analyzed [25].…”

Cognitive dysfunction with aging and the role of inflammation

“…It is interesting to note that one recent study [Grigoleit et al 2010] tested the effects of LPS administration on healthy humans. The authors tested 12 healthy men before and after the intravenous administration of 0.4 ng/kg LPS.…”

“…As noted above, inflammation is associated with many disease states which may affect physical functioning independently of inflammation. True experimental designs are for the most part impractical and unethical in humans, with the study of Grigoleit and colleagues reviewed above, as one notable exception [Grigoleit et al 2010]. Therefore, animal models are essential for determining whether inflammation can in fact cause cognitive impairment and disability.…”