Hamdan Medical Journal (previously the Journal of Medical Sciences)

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From TNF and IL-1 to IL-17: The Destructive Cytokine Network in Rheumatoid Arthritis

Pierre Miossec
Published in : Journal of Medical Sciences ; Vol 1, No 1 (2008)
DOI : 10.2174/1996327000801010017


Although its precise etiology remains unknown, examination of the inflammatory synovium in rheumatoid arthritis (RA) shows complex interactions involving cell contacts and soluble mediators, namely cytokines. Over the years and starting in 1983, the work of Miossec and colleagues has focused on the role of these interactions in the unbalanced equilibrium in favor of inflammation and destruction with emphasis on the regulatory effect of T cell subsets and their derived cytokines to dissect the communication network inside the synovium.

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Miossec P, Dinarello CA, Ziff M. Interleukin-1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid. Arthritis Rheum, 1986; 29: 461-470.

Miossec P, Cavender D, Ziff M. Production of interleukin 1 by human endothelial cells. J Immunol, 1986; 136: 2486-2491.

Miossec P, Ziff M. Immune interferon enhances the production of interleukin 1 by human endothelial cells stimulated with lipopolysaccharide. J lmmunol, 1986; 137: 2848-2852.

Cavender D, Haskard D, Yu CL, Iguchi T, Miossec P, Oppenheimer-Marks N, et al. Pathways to chronic inflammation in rheumatoid synovitis. Fed Proc, 1987; 46: 113-117.

Jouvenne P, Fossiez F, Garrone P, Djossou O, Banchereau J, Miossec P. Increased incidence of neutralizing autoantibodies against interleukin-1 alpha (IL-1 alpha)

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Jouvenne P, Fossiez F, Banchereau J, Miossec P. High levels of neutralizing autoantibodies against IL-1 alpha are associated with a better prognosis in chronic

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Jouvenne P, Vannier E, Dinarello CA, Miossec P. Elevated levels of soluble interleukin-1 receptor type IT and interleukin-1 receptor antagonist in patients with chronic arthritis: correlations with markers of inflammation and joint destruction. Arthritis Rheum, 1998; 41: 1083-1089.

Jouvenne P, Chaudhary A, Buchs N, Giovine FS, Duff GW, Miossec P. Possible genetic association between interleukin-1 alpha gene polymorphism and the severity of chronic polyarthritis. Eur Cytokine Netw, 1999; 10: 33-36.

Buchs N, di Giovine FS, Silvestri T, Vannier E, Duff GW, Miossec P. IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interaction with their plasma levels. Genes Immunol, 2001; 2: 222-228.

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Miossec P, Briolay J, Dechanet J, Wijdenes J, Martinez- Valdez H, Banchereau J. Inhibition of the production of pro inflammatory cytokines and immunoglobulins by

interleukin-4 in an ex vivo model of rheumatoid synovitis. Arthritis Rheum, 1992; 35: 874-883.

Buchs N, Silvestri T, di Giovine FS, Chabaud M, Vannier E, Duff GW, Miossec P. IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction. Rheumatology (Oxford), 2000; 39:1126-1131.

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Chomarat P, Vannier E, Dechanet J, Rissoan MC, Banchereau J, Dinarello CA, Miossec P. Balance of IL-1 receptor antagonistJIL-1 beta in rheumatoid synovium and its regulation by IL-4 and IL-10. J Immunol, 1995; 154: 1432-1439.

Briolay J, Dechanet J, Blanchard D, Banchereau J, Miossec P. Interleukin 4 inhibits polyclonal immunoglobulin secretion and cytokine production by peripheral blood

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Chomarat P, Briolay J, Banchereau J, Miossec P. Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin-4. Arthritis Rheum, 1993; 36: 234-242.

Haddad A, Bienvenu J, Miossec P. Increased production of a Th2 cytokine profile by activated whole blood cells from rheumatoid arthritis patients. J Clin Immunol , 1998; 18: 399-403.

Dechanet J, Briolay J, Rissoan MC, Chomarat P, Galizzi JP, Banchereau J, et al. IL-4 inhibits growth factor-stimulated rheumatoid synoviocyte proliferation by blocking the early phases of the cell cycle. J Immunol, 1993; 151: 4908-4917.

Dechanet J, M. Rissoan MC, Banchereau J, Miossec P. Interleukin 4, but not interleukin 10, regulates the production of inflammation mediators by rheumatoid synoviocytes. Cytokine, 1995; 7: 176-183.

Miossec P, Chomarat P, Dechanet J, Moreau JF, Roux JP, Delmas P, et al. Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammatory

cytokines in an ex vivo model of bone resorption in rheumatoid arthritis. Arthritis Rheum, 1994; 37: 1715-1722.

Quayle AJ, Chomarat P, Miossec P, Kjeldsen-Kragh J, Forre O, Natvig JB. Rheumatoid inflammatory T-cell clones express mostly Th1 but also Th2 and mixed (Th0- like) cytokine patterns. Scand J Immuno1, 1993; 38: 75- 82.

Chomarat P, Kjeldsen-Kragh J, Quayle AJ, Natvig JB, Miossec P. Different cytokine production profiles of gamma delta T cell clones: relation to inflammatory

arthritis. Eur J Immunol, 1994; 24: 2087-2091.

Chomarat P, Rissoan MC, Banchereau J, Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med, 1993; 177: 523-527.

Chomarat P, Banchereau J, Miossec P. Differential effects of interleukins 10 and 4 on the production of interleukin-6 by blood and synovium monocytes in rheumatoid

arthritis. Arthritis Rheum, 1995; 38: 1046-1054.

Miossec P, Chomarat P, Dechanet J. Bypassing the antigen to control rheumatoid arthritis. Immunol Today, 1996; 17: 170-173.

Miossec P, van den Berg W. 1997. Thl/fh2 cytokine balance in arthritis. Arthritis Rheum, 1997; 40: 2105-2115.

Miossec P. Are T cells in rheumatoid synovium aggressors or bystanders? Curr Opin Rheumatol, 2000; 12(3):181-5.

Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, et al. Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid

synovium. Arthritis Rheum, 1999; 42: 963-970.

Aarvak T, Chabaud M, Miossec P, Natvig JB. JL-17 is produced by some proinflammatory Thl/Th0 cells but not by Th2 cells. J Immunol, 1999; 162: 1246-1251.

Chabaud M, Fossiez F, Taupin JL, Miossec P. Enhancing effect of IL-17 on IL-l-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol, 1998;161: 409-414.

Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P. Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine,

; 12: 1092-1099.

Chabaud M, Aarvak T, Garnero P, Natvig JB, Miossec P. Potential contribution of IL-17 -producing Th (1) cells to defective repair activity in joint inflammation: partial correction with Th (2)-promoting conditions. Cytokine, 2001; 13: 113-118.

Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P. IL 17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid

arthritis. Arthritis Res, 2001; 3: 168-177.

Aarvak T, Chabaud M, Kallberg E, Miossec P, Natvig JB. Change in the Th1/Th2 phenotype of memory Tcell clones from rheumatoid arthritis synovium. Scand J Immunol, 1999; 50: 1-9.

Lubberts E, Joosten LA, Chabaud M, van Den Bersselaar L, Oppers B, Coenen-De Roo CJ, et al. IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and

osteoprotegerin ligand and prevents bone erosion. J Clin Invest, 2000; 105: 1697-1710.

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Chabaud M, Miossec P. The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling

synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum, 2001; 44: 1293-1303.

Granet C, Miossec P. Combination of the proinflammatory cytokines IL-1, TNF-alpha and IL-17 leads to enhanced expression and additional recruitment of AP-

family members, Egr-1 and NF-kappaB in osteoblastlike cells. Cytokine, 2004; 26: 169-177.

Granet C, Maslinski W, Miossec P. Increased AP-1 and NF-kappaB activation and recruitment with the combination of the proinflammatory cytokines IL-1 beta, tumor necrosis factor alpha and IL-17 in rheumatoid synoviocytes. Arthritis Res Ther, 2004; 6: R190-198.

Chevrel G, Granet C, Miossec P. Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6 production, NF-kappaB nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors. Ann Rheum Dis, 2005; 64: 1257-1262.

Page G, Lebecque S, Miossec P. Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine

expression in rheumatoid synovium. J Immunol 2002; 168: 5333-5341.

Page G, Miossec P. Paired synovium and lymph nodes from rheumatoid arthritis patients differ in dendritic cell and chemokine expression. J Pathol, 2004; 204: 28-38.

Chabaud M, Page G, Miossec P. Enhancing effect of IL- 1, IL-17, and TNF-alpha on macrophage inflammatory protein-3alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines. J Immunol, 2001; 167: 6015-6020.

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response to infliximab in a large rheumatoid arthritis population. Ann Rheum Dis, 2006; 65(3): 342-7.

Marotte H, Maslinski W, Miossec P. Circulating tumour necrosis factor-alpha bioactivity in rheumatoid arthritis patients treated with infliximab: link to clinical response. Arthritis Res Ther, 2005; 7: R149-155.

Kawashima M, Miossec P. mRNA Quantification of Tbet, GATA-3, IFN-gamma, and IL-4 Shows a Defective Th1 Immune Response in the Peripheral Blood from Rheumatoid Arthritis Patients: Link with Disease Activity. J Clin lmmunol, 2005; 25: 209-214.

Kawashima M, Miossec P. Effect of treatment of rheumatoid arthritis with infliximab on IFN gamma, IL-4, T-bet, and GATA-3 expression: link with improvement of

systemic inflammation and disease activity. Ann Rheum Dis, 2005; 64: 415-418.

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