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IL-32, a proinflammatory cytokine in rheumatoid arthritis

2006; National Academy of Sciences; Volume: 103; Issue: 9 Linguagem: Inglês

10.1073/pnas.0511233103

1091-6490

Leo A. B. Joosten, Mihai G. Netea, Soohyun Kim, Do‐Young Yoon, Birgitte Oppers‐Walgreen, Timothy R. D. J. Radstake, Pilar Barrera, Fons A. J. van de Loo, Charles A. Dinarello, Wim B. van den Berg,

Rheumatoid Arthritis Research and Therapies

IL-32 is a recently discovered cytokine that induces TNFα, IL-1β, 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 TNFα ( R = 0.68 and P < 0.004), IL-1β ( 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-32γ into the knee joints of naïve mice, joint swelling, with pronounced influx of inflammatory cells and cartilage damage, was observed. In TNFα-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, TNFα-dependent. IL-32, strongly associated with TNFα, IL-1β, and IL-18, appears to play a role in human RA and may be a novel target in autoimmune diseases.