A role for IL-18 in neutrophil activation

Leung, B. P., Culshaw, S. , Gracie, J. A., Hunter, D., Canetti, C. A., Campbell, C., Cunha, F., Liew, F. Y. and McInnes, I. B. (2001) A role for IL-18 in neutrophil activation. Journal of Immunology, 167, pp. 2879-2886. (doi: 10.4049/jimmunol.167.5.2879) (PMID:11509635)

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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 (α and β) 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-α production. Together, these data define a novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Prof Foo and Culshaw, Professor Shauna and Leung, Dr Bernard and Gracie, Professor Alastair
Authors: Leung, B. P., Culshaw, S., Gracie, J. A., Hunter, D., Canetti, C. A., Campbell, C., Cunha, F., Liew, F. Y., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Immunology

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