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Title: The role of IL-17 in inflammatory hyperalgesia
Author: McNamee, Kay Edwina
ISNI:       0000 0004 2707 4317
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects up to 1% of the population. The importance of tumour necrosis factor (TNF) in RA has been established and anti-TNF biologics have proved to be highly effective in reducing inflammation. However, a proportion of RA patients fail to adequately respond to anti-TNF and even those who do respond have residual pain. This has prompted the investigation into other cytokines, such as interleukin-17 (IL-17), as potential new targets. This study sought to investigate the contribution of IL-17 to acute or chronic hyperalgesia. C57BL/6 mice were injected with recombinant IL-17. This induced a transient hyperalgesia, which was found to be dependent both on neutrophil migration and signalling through TNFR1. Using the air pouch model of cell migration, it was confirmed that the cell infiltration was associated with increased expression of the chemokine keratinocyte attractant (KC). These results suggest that IL-17 induces acute hyperalgesia by inducing TNF from resident cells. To investigate IL-17 and chronic hyperalgesia, the collagen induced arthritis mouse model (CIA) was used. IL-17RA was found to be up regulated in both the paw and in the dorsal root ganglia in arthritis, suggesting a role for IL-17 in chronic hyperalgesia. IL-17 blockade proved to be anti-arthritic and analgesic during CIA and potently reduced expression of pro-inflammatory cytokines. This study confirms that IL-17 contributes to acute and chronic hyperalgesia but acts in part via the induction of TNF.
Supervisor: Inglis, Julia ; Anand, Praveen ; Williams, Richard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral