Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models.
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.
Department of Pediatrics, University of California at San Diego, La Jolla, CA 92093, USA.
Matthew D
MD
McGeough
Carla A
CA
Pena
James L
JL
Mueller
Derek A
DA
Pociask
Lori
L
Broderick
Hal M
HM
Hoffman
Susannah D
SD
Brydges
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D056587:Cryopyrin-Associated Periodic Syndromes / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D018390:Gene Targeting; D016130:Immunophenotyping; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D053583:Interleukin-1beta / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015203:Reproducibility of Results
D015415:Biomarkers; D002352:Carrier Proteins; C508600:IL6 protein, human; D058847:Inflammasomes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse