Defining the therapeutic role of IL-10 in African Trypanosomiasis. (360G-Wellcome-082786_B_07_Z)

£240,231

This project will determine the neuroprotective role of the counter-inflammatory cytokine Interleukin-10 (IL-10) in human African trypanosomiasis (HAT) and evaluate the potential of this cytokine as a therapeutic and diagnostic tool. Our core hypothesis is that IL-10 plays the key role in reducing neuroinflammatory responses in HAT, thereby prolonging survival. The hypothesis leads to the following predictions, which we will test: 1. IL-10 administration parenterally in a mouse model wil l ameliorate neuropathology, and may delay or restrict invasion of the brain parenchyma by trypanosomes. 2. Blocking IL-10 signalling in astrocytes in trypanosome-infected mice will exacerbateCNS neuropathology 3. IL-10 levels in the CSF of HAT patients will inversely correlate with disease severity. Further to these predictions, the proposed project aims to answer the following questions: 1. Does IL-10 administration prevent the neuroinflammatory reaction in the mouse model? 2. What is th e cellular source of IL-10 in the CNS? 3. Is the pattern of trypanosome invasion of the CNS altered following IL-10 administration? 4. Is the astrocyte the key cell type through which IL-10 modulates the CNS inflammatory reaction? 5. Are IL-10, and astrogliosis marker levels in the serum and CSF of trypanosomiasis patients dignostic for disease severity and potential staging tools?

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Grant Details

Amount Awarded 240231
Applicant Surname Sternberg
Approval Committee Tropical and Clinical Immunology and Infectious Disease Funding Committee
Award Date 2007-05-15T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project funding: Inactive scheme
Internal ID 082786/B/07/Z
Lead Applicant Dr Jeremy Sternberg
Other Applicant(s) Dr Jean Rodgers, Prof Peter Kennedy
Partnership Value 240231
Planned Dates: End Date 2012-06-30T00:00:00+00:00
Planned Dates: Start Date 2008-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland