GENESIS OF FEVER · Homeostasis during fever and inflammation: A Role of Epoxygenase
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-05-01 → 2007-04-30
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Results in brief
Final Activity Report Summary - GENESIS OF FEVER (Homeostasis during fever and inflammation: a role of epoxygenase)
The Marie-Curie international reintegration grant, which was allocated via the MIRG-CT-2004-006152 contract, aimed to transfer my research from the United States of America to the Nicolas Copernicus University (NCU) in Torun (Poland). Investigation on the mechanism of fever and inflammation was conducted by me in the United States of America research institutions, such as the University of Michigan, Lovelace Research Institute and Medical College of Georgia, for circa 15 years. Thanks to the support of the European Commission, the Department of Immunology was founded within the structure of NCU to host the laboratory equipment transferred from the United States in order to continue research and start the education and other scientific activities. The initiative to organise the laboratory of immunology and specific animal facility to maintain the research outlined in the proposal was successful, resulting in two PhD projects, which started in 2006, nine MSc projects completed in 2006 and 2007, and 11 undergraduate, i.e. bachelor licensee degree, projects completed within this referred time period. The following general aspects of fever and inflammation were elaborated by students of all three levels and staff of the Department of Immunology: 1. pyrogenic and inflammatory actions of bacterial lipopolysaccharides and unmethylated cytosine guanine deoxyribonucleic acid (CpG-DNA) motifs in mice and rats; 2. expression of certain cytokine transcripts, namely interleukin-6 and tumor necrosis factor, in macrophages upon stimulation with pyrogens; 3. modulating effect of epoxygenase, heme oxygenase and epoxide hydrolase on the prostaglandin-dependent and cytokine-dependent mechanism of fever; 4. modulating effect of hypoxia conditioning on cyclooxygenases involved in the fever and inflammation; 5. significance of the intracellular signalling pathway involving toll-like receptors, nuclear factor kappa B and myeloid differentiation factor 88 in the genesis of fever; and 6. implementation of the biotelemetry in studying sickness behaviour using small laboratory mammals such as rats and mice.
Data: CORDIS, © European Union
Project objective
OBJECTIVE: The ultimate goal of the proposed research is to understand mechanisms involved in limiting the magnitude of the febrile response during infection. A specific aim is to continue a laboratory research on the mechanisms involving epoxygense in controlling fever and inflammation. BACKGROUND: Fever is a neuroimmunomodulatory response mediated by pro-inflammatory cytokines, synthesis of which is activated by bacterial, viral, fungal, and other infectious factors. Principal mechanism of fever involv es a cytokine-provoked liberation of arachidonic acid from cell membranes and induction of cyclooxygenase-2 (COX-2) in cells. Subsequently, COX-2 converts arachidonic acid into prostaglandins. These are molecular events that are also fundamental to the inflammatory processes. JUSTIFICATION: It is well known that exacerbated fever can be harmful.Clinical data indicate, however, that fever's magnitude very rarely reaches unsafe high measures. But what keeps fever from reaching dangerous heights? The proposer's study initiated in the USA revealed that epoxyeicosanoids, i.e., products of the metabolism of arachidonic acid via epoxygenases (an alternative enzyme system to COX-2), act as endogenous antipyretic and anti-inflammatory factors. Recent data fro m the proposer's laboratory indicate that epoxyeicosanoids reduce the activity of COX-2, which mimics a well-known action of the aspirin-like drugs. These data suggest that epoxyeicosanoids represent a homeostatic mechanism upon inflammation.An overall hypothesis has been put forward that this endogenous mechanism operates during sickness to set the limits of the immune response, preventing the inflammatory components from reaching a detrimental over-expression. SIGNIFICANCE: A new concept is emerging t hat modulation of this homeostatic process may be included into the current repertoire of prophylaxis, immunotherapy, and treatment of the acute and chronic inflammatory disorders.
Original text from CORDIS.
Participants
- UNIWERSYTET MIKOLAJA KOPERNIKA · TORUNCoordinatorPoland
Links
Data: CORDIS, © European Union