Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase regulate induction of Mcl-1 and survival in glucocorticoid-treated human neutrophils

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

“…PI3K is another key signal transducer for neutrophil survival (43,44). Induction of neutrophil survival by various antiapoptotic factors such as GM-CSF, IL-8, interferon (IFN)-β and LPS has been reported to occur through the PI3K pathway (45)(46)(47).…”

“…PI3K-mediated Akt activity can lead to prosurvival phosphorylation of Bax (48). Furthermore, glucocorticoids have been shown to inhibit neutrophil apoptosis, and this effect of glucocorticoids was found to be mediated in part by signaling through PI3K (43). PI3K activation following burn injury results in a downstream activation of nuclear factor-κB and Bad phosphorylation in neutrophils.…”

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1β synthesis by human neutrophils

“…Recent work has demonstrated that GCS are able to induce proinflammatory responses in these cells [20][21][22][23][24][25][26]. We tested the hypothesis that GCS affect TNF-a-induced synthesis and secretion of pro-and anti-inflammatory cytokines by neutrophils.…”

“…However, despite the strong capacity of GCS to inhibit inflammation, inhibition of neutrophil-driven inflammation seems to be less effective [19]. Other studies have shown that GCSs elicit proinflammatory effects on granulocytes, such as increased interleukin (IL)-1 receptor (IL-1R) type I expression on human neutrophils [20], prolonged neutrophil survival in vitro [21,22], leukocytosis in vivo [23], p38 activation in neutrophils and eosinophils [24,25], increased immunoglobulin A binding by eosinophils [25], and increased secretion of lysosomal enzymes by neutrophils [26]. Because not only proinflammatory, but also anti-inflammatory, mediators are controlled by the transcription factor NF-kB, GCSs would be expected to affect the expression of anti-inflammatory response as well, which is not often assessed.…”

Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials

“…Metabolism of methylprednisolone, used in many clinical trials of severe CAP, appears to be particularly responsive to the inhibitory effects of clarithromycin on CYP3A4, while metabolism of prednisone is apparently unaffected (21). Furthermore, another property of macrolides which needs to be considered in the setting of CS adjunctive therapy of CAP is the suppressive effects of these agents on neutrophils, cells which are apparently insensitive to the direct antiinflammatory actions of CS (17,22,23). Therefore, although the current literature is limited, the influence of concomitant macrolide administration, whether beneficial, detrimental or negligible, on CS metabolism, may be an issue which requires serious consideration when evaluating the outcome of most clinical trials investigating the role of adjuvant CS in severe CAP.…”