Updating evidence role corticosteroids severe sepsis septic shock

Third, systemic inflammation may cause breakdown to the BBB, facilitating blood-borne cytokines traffic to deep brain structures (13–16).Among the various factors that contribute to the disruption of tight junctions or swelling of the BBB, the complement system, particularly C5a anaphylatoxin expressed both by astrocytes and endothelial cells, may play a key role (17).For example, IL-1 and TNF are likely the two main mediators of the so-called sickness behavior, whereas IL-6 may have no apparent direct effect on behavior (21).Experiments in animals suggest that TNF- and IL-1-induced release of corticosterone is CRH-dependent mechanism (22, 23), whereas IL-6 may stimulate adrenal function by both CRH-dependent and -independent mechanisms (24).During stress, the HPA axis is mainly activated by CRH-independent pathways, involving immune mediators.

Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response.Similarly, in patients with septic shock, postmortem examination suggested overexpression of IL-1 and TNF in hypothalamic nuclei (20).Different cytokines in different brain regions induce different brain responses.There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection.These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol.

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