Redox distress and genetic defects conspire in systemic autoinflammatory diseases

Georg Varga, Marco Gattorno, Dirk Foell, Anna Rubartelli

Research output: Contribution to journalArticle

Abstract

Inflammation is initiated by innate immune cell activation after contact with pathogens or tissue injury. An increasing number of observations have suggested that cellular stress, in the absence of infection or evident damage, can also induce inflammation. Thus, inflammation can be triggered by exogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) - so-called classic inflammation - or by endogenous stress resulting from tissue or cellular dysfunction. External triggers and cellular stress activate the same molecular pathways, possibly explaining why classic and stress-induced inflammation have similar clinical manifestations. In some systemic autoinflammatory diseases (SAIDs), inflammatory cells exhibit reduction-oxidation (redox) distress, having high levels of reactive oxygen species (ROS), which promote proinflammatory cytokine production and contribute to the subversion of mechanisms that self-limit inflammation. Thus, SAIDs can be viewed as a paradigm of stress-related inflammation, being characterized by recurrent flares or chronic inflammation (with no recognizable external triggers) and by a failure to downmodulate this inflammation. Here, we review SAID pathophysiology, focusing on the major cytokines and DAMPs, and on the key roles of redox distress. New therapeutic opportunities to tackle SAIDs by blocking stress-induced pathways and control the response to stress in patients are also discussed.

Original languageEnglish
Pages (from-to)670-680
Number of pages11
JournalNature Reviews Rheumatology
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

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Oxidation-Reduction
Inflammation
Cytokines
Reactive Oxygen Species
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Rheumatology

Cite this

Redox distress and genetic defects conspire in systemic autoinflammatory diseases. / Varga, Georg; Gattorno, Marco; Foell, Dirk; Rubartelli, Anna.

In: Nature Reviews Rheumatology, Vol. 11, No. 11, 01.11.2015, p. 670-680.

Research output: Contribution to journalArticle

Varga, Georg ; Gattorno, Marco ; Foell, Dirk ; Rubartelli, Anna. / Redox distress and genetic defects conspire in systemic autoinflammatory diseases. In: Nature Reviews Rheumatology. 2015 ; Vol. 11, No. 11. pp. 670-680.
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