Research ArticleSepsis

Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis

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Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaau5266
DOI: 10.1126/scitranslmed.aau5266

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Sigma-1 receptor subdues systemic inflammation

Systemic inflammation can be lethal, as in the case of septic shock. Rosen et al. hypothesized that the endoplasmic reticulum, now understood to affect inflammation, could be an untapped therapeutic target. They found that mice lacking the endoplasmic reticulum sigma-1 receptor had exacerbated responses to LPS or fecal slurry. The antidepressant fluvoxamine can bind sigma-1 and acts as an agonist. Therapeutic treatment of mice in the two inflammatory models revealed that fluvoxamine lowered inflammatory cytokine production and improved survival. Their results suggest that repurposing fluvoxamine to enhance sigma-1 activity may be beneficial for treating sepsis.