Abstract
IL-6 is a known downstream target of IL-1β and is consistently increased in serum from patients with NLRP3 inflammasome-mediated conditions. Therefore, IL-6 could be a therapeutic target in the treatment of IL-1β-provoked inflammation. IL-6 was increased in serum with accompanying neutrophilia in tissues of an inducible mouse model of Muckle-Wells syndrome. However, an IL-6-null background failed to provide phenotypic rescue and did not significantly impact inflammatory cytokine levels. In a second model of IL-1β-driven inflammation, NLRP3 activation by monosodium urate crystals similarly increased IL-6. Consistent with our Muckle-Wells syndrome model, ablation of IL-6 did not impact an acute neutrophilic response in this in vivo evaluation of gouty arthritis. Taken together, our results indicate that IL-6 is a reliable marker of inflammation, with no direct role in inflammasome-mediated disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers / metabolism
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Carrier Proteins* / metabolism
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Carrier Proteins* / physiology
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Cryopyrin-Associated Periodic Syndromes / immunology
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Cryopyrin-Associated Periodic Syndromes / metabolism
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Cryopyrin-Associated Periodic Syndromes / therapy
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Disease Models, Animal*
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Gene Knock-In Techniques
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Gene Targeting
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Immunophenotyping
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Inflammasomes* / genetics
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Inflammasomes* / metabolism
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Inflammasomes* / physiology
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Inflammation Mediators / metabolism*
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Inflammation Mediators / physiology
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Interleukin-1beta / genetics
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Interleukin-1beta / physiology
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Interleukin-6 / deficiency
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Interleukin-6 / metabolism*
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Interleukin-6 / physiology
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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NLR Family, Pyrin Domain-Containing 3 Protein
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Reproducibility of Results
Substances
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Biomarkers
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Carrier Proteins
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IL6 protein, human
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Inflammasomes
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Inflammation Mediators
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Interleukin-1beta
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Interleukin-6
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Nlrp3 protein, mouse