TY - JOUR
T1 - IL-32, a proinflammatory cytokine in rheumatoid arthritis
AU - Joosten, Leo A.B.
AU - Netea, Mihai G.
AU - Kim, Soo Hyun
AU - Yoon, Do Young
AU - Oppers-Walgreen, Birgitte
AU - Radstake, Timothy R.D.
AU - Barrera, Pilar
AU - Van De Loo, Fons A.J.
AU - Dinarello, Charles A.
AU - Van Den Berg, Wim B.
PY - 2006/2/28
Y1 - 2006/2/28
N2 - 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 E2 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.
AB - 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 E2 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.
KW - Autoimmune
KW - Inflammation
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=33644765841&partnerID=8YFLogxK
U2 - 10.1073/pnas.0511233103
DO - 10.1073/pnas.0511233103
M3 - Article
C2 - 16492735
AN - SCOPUS:33644765841
SN - 0027-8424
VL - 103
SP - 3298
EP - 3303
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 9
ER -