Regulation Of Leukocyte Trafficking By Macrophage Migration Inhibitory Factor (MIF).
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The entry of white blood cells in to tissues is a primary event which drives tissue and organ damage in a number of inflammatory and immune mediated conditions. Diseases as diverse as rheumatoid arthritis, lupus or shock due to bacterial infection (septic shock) have many different triggers and manifestations. However almost all autoimmune and inflammatory diseases have one common feature: white blood cells must leave the blood and enter tissue in order to cause tissue inflammation and ultimatel ....The entry of white blood cells in to tissues is a primary event which drives tissue and organ damage in a number of inflammatory and immune mediated conditions. Diseases as diverse as rheumatoid arthritis, lupus or shock due to bacterial infection (septic shock) have many different triggers and manifestations. However almost all autoimmune and inflammatory diseases have one common feature: white blood cells must leave the blood and enter tissue in order to cause tissue inflammation and ultimately tissue damage and loss of function. The mechanism whereby white blood cells leave the blood stream and cross blood vessel walls to get into tissues is a multi-step process often referred to as white blood cell trafficking. Most of the current treatments for immune and inflammatory conditions have the primary aim of keeping white blood cells out of tissue in order to prevent damage. Some of these treatments, like steroids (cortisone), are very effective but cannot be used for prolonged periods because of the risk of problems like bone thinning (osteoporosis), high blood pressure or diabetes. Other treatments and immunosuppressive agents can also be effective but are themselves associated with toxicity and risk of organ damage. Although substantial progress has been made in the management of immune and inflammatory conditions in the last 50 years, the current treatment options are far from ideal. Macrophage migration inhibitory factor (MIF) is an inflammatory substance released by cells which comprise the blood vessel wall as well as by white blood cells themselves. It is known to contribute to the build up of white blood cells in inflamed tissue. The effect of MIF on white blood cell trafficking has never been examined. Understanding how MIF promotes white cell entry in to tissues could be crucial in our understanding of this important process and blocking MIF may prove to be a useful and effective way to prevent it.Read moreRead less
Macrophage Migration Inhibitory Factor (MIF): Pathological And Therapeutic Significance In Post- Infarct Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$547,577.00
Summary
Ischemic heart injury mediated by the inflammatory response has a significant impact on the prognosis. MIF is a central factor mediating and amplifying the inflammatory response but its role in heart disease remains largely untested. This project will study, for the first time, the crucial role of MIF in ischemic heart disease and will establish important experimental evidence for developing new anti-inflammation therapeutic strategies against ischemic heart injury.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
In this study, mouse models of disease will be used to determine the mechanisms by which the proinflammatory molecule called MIFpromotes the development of insulin resisitance and type 2 diabetes. We will also test whether therapeutic blockade of MIF can prevent the progression of disease in mice with established type 2 diabetes. Studies on tissue samples obtained from human patients will be used to confirm the human relevance of these findings.