A Role for IL-18 in Neutrophil Activation
Bernard P. Leung,Shauna Culshaw,J. Alastair Gracie,David Hunter,Claudio Canetti,Carol Campbell,Fernando Q. Cunha,Foo Y. Liew,Iain B. McInnes +8 more
TLDR
A novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses is defined and is defined by the capacity to release cytokine and chemokine in neutrophil derived from rheumatoid arthritis synovial fluid.Abstract:
IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during early innate immune responses, we have explored the capacity of IL-18 to activate neutrophils. Human peripheral blood-derived neutrophils constitutively expressed IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL-18. IL-18 induced cytokine and chemokine release from neutrophils that was protein synthesis dependent, up-regulated CD11b expression, induced granule release, and enhanced the respiratory burst following exposure to fMLP, but had no effect upon the rate of neutrophil apoptosis. The capacity to release cytokine and chemokine was significantly enhanced in neutrophils derived from rheumatoid arthritis synovial fluid, indicating differential responsiveness to IL-18 dependent upon prior neutrophil activation in vivo. Finally, IL-18 administration promoted neutrophil accumulation in vivo, whereas IL-18 neutralization suppressed the severity of footpad inflammation following carrageenan injection. The latter was accompanied by reduction in tissue myeloperoxidase expression and suppressed local TNF-alpha production. Together, these data define a novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses.read more
Citations
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IL‐1, IL‐18, and IL‐33 families of cytokines
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The Sterile Inflammatory Response
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Neutrophil cell surface receptors and their intracellular signal transduction pathways
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Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development?
Waldiceu A. Verri,Thiago M. Cunha,Carlos Amílcar Parada,Stephen Poole,Fernando Q. Cunha,Sérgio H. Ferreira +5 more
TL;DR: The evidence suggesting pro- and anti-inflammatory cytokines and chemokines are potential targets to develop novel drugs and therapies for the treatment of pain is emphasized, emphasizing the importance of the direct and indirect actions of cytokine actions in inflammatory and neuropathic hypernociception.
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Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span
Ian Sabroe,Lynne R. Prince,Elizabeth C. Jones,Malcolm J. Horsburgh,Simon J. Foster,Stefanie N. Vogel,Steven K. Dower,Moira K. B. Whyte +7 more
TL;DR: TLR4 signaling presents itself as a pharmacological target that may allow therapeutic modulation of neutrophil survival by direct and indirect mechanisms at sites of inflammation.
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Kiyoshi Takeda,Hiroko Tsutsui,Tomohiro Yoshimoto,Osamu Adachi,Nobuaki Yoshida,Tadamitsu Kishimoto,Haruki Okamura,Kenji Nakanishi,Shizuo Akira +8 more
TL;DR: The in vivo role of IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response is demonstrated, demonstrating the important role of both IL- 18 andIL-12 as cytokine secreted from activated macrophages and induces IFNgamma production.
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Interleukin-18 Binding Protein: A Novel Modulator of the Th1 Cytokine Response
Daniela Novick,Soohyun Kim,Giamila Fantuzzi,Leonid L. Reznikov,Charles A. Dinarello,Menachem Rubinstein +5 more
TL;DR: Interleukin-18 binding protein functions as an inhibitor of the early Th1 cytokine response, suggesting that viral products may attenuate IL-18 and interfere with the cytotoxic T cell response.