IL-32, a proinflammatory cytokine in rheumatoid arthritis.
IL-32 is a recently discovered cytokine that induces TNFalpha, IL-1beta, IL-6, and chemokines. We investigated whether IL-32 is expressed in the synovia of patients with rheumatoid arthritis (RA) and studied associations with disease severity and the presence of other cytokines. Immunohistochemistry revealed that IL-32 is highly expressed in RA synovial tissue biopsies, whereas IL-32 was not observed in synovial tissues from patients with osteoarthritis. Moreover, in synovial biopsies from 29 RA patients with active disease, the level of IL-32 staining correlated with erythrocyte sedimentation rate, a marker of systemic inflammation (R = 0.63 and P < 0.0003). Synovial staining of IL-32 also correlated with indices of synovial inflammation (R = 0.80 and P < 0.0001) as well as synovial presence of TNFalpha (R = 0.68 and P < 0.004), IL-1beta (R = 0.79 and P < 0.0001), and IL-18 (R = 0.82 and P < 0.001). IL-32 was a potent inducer of prostaglandin E(2) release in mouse macrophages and human blood monocytes, an important property for inflammation. After the injection of human IL-32gamma into the knee joints of naïve mice, joint swelling, with pronounced influx of inflammatory cells and cartilage damage, was observed. In TNFalpha-deficient mice, IL-32-driven joint swelling was absent and cell influx was markedly reduced, but loss of proteoglycan was unaffected, suggesting that IL-32 activity is, in part, TNFalpha-dependent. IL-32, strongly associated with TNFalpha, IL-1beta, and IL-18, appears to play a role in human RA and may be a novel target in autoimmune diseases.
Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, The Netherlands.
Leo A B
LA
Joosten
Mihai G
MG
Netea
Soo-Hyun
SH
Kim
Do-Young
DY
Yoon
Birgitte
B
Oppers-Walgreen
Timothy R D
TR
Radstake
Pilar
P
Barrera
Fons A J
FA
van de Loo
Charles A
CA
Dinarello
Wim B
WB
van den Berg
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D007596:Joints / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C496971:IL32 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D020382:Interleukin-18; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha