The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes

Article Article scientifique Article The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes eng 2006 author Magne David 562536 author Palmer-Lourenco Gaby 0000-0001-7567-1798 45743 author Barton Jenny L author Mezin Françoise 23110 author Talabot-Ayer Dominique author Bas Sylvette 25547 author Duffy Trevor 626737 author Noger Marcus author Guerne Pierre-André 29463 author Nicklin Martin J H author Gabay Cem 70978 R80 10.1186/ar1946 16646978 1478-6354 Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1beta protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis. Animals Arthritis, Rheumatoid/blood/immunology Cartilage, Articular/drug effects/immunology Chondrocytes/drug effects/immunology Fibroblasts/immunology Humans Inflammation/immunology Interleukin-1/blood/immunology Joints/immunology Mice Synovial Fluid/cytology/immunology Dewey 616 Dewey 617 56 Département de médecine 221 57 Département de chirurgie 222 false 74 Chirurgie orthopédique et traumatologique 98 28 Inflammation articulaire 44 Arthritis research & therapy 8 3 d3891ca3-2cf8-4bce-bbc9-ed82cf4e8cc6 Article (Published version) Public ar1946.pdf 416661 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département de chirurgie

Title	Published in	Access level	OA Policy	Year	Views	Downloads

The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes	Arthritis research & therapy			2006	591	368

Archive ouverte UNIGE

Duffy, Trevor