To the Editor: Dr Iwashyna and colleagues demonstrated high rates of new-onset cognitive and functional impairments among elderly survivors of severe sepsis.1 Converging evidence from human and preclinical studies suggests such consequences of sepsis may be associated with the effects of the immune system on the brain.
Proinflammatory cytokines (ie, interleukins and tumor necrosis factor) released as result of inflammation can reach the brain in a number of ways: via peripheral afferents (ie, the vagus nerve), entry through leaky circumventricular areas in the blood-brain barrier, or active transport.2 Once in the brain, the cytokine signal stimulates microglia to secrete inflammatory mediators (ie, cytokines, chemokines, and proteases) from its monocytes and macrophages.3 These local inflammatory mediators can affect neuronal function and synaptic plasticity by increasing oxidative stress and weakening astrocytic tight junctions.3 They also increase metabolism and reuptake of neurotransmitters (ie, serotonin, noradrenalin, and dopamine) and stimulate the hypothalamic-pituitary-adrenal axis.2 We believe this may explain the occurrence of a range of cognitive and affective problems observed in sepsis survivors. In healthy volunteers, immune activation has been shown to increase circulating cytokines, induce anxiety and low mood, and decrease cognitive performance.4
Khandaker GM, Jones PB. Cognitive and Functional Impairment After Severe Sepsis. JAMA. 2011;305(7):673-674. doi:10.1001/jama.2011.142