The Experimental Pathology Department within the William Harvey Research Institute is devoted to the study of inflammatory processes and their impact on tissue function. The aim is to better understand the pathogenesis of diseases such as rheumatoid arthritis and to identify novel therapeutic targets. The department brings a multidisciplinary approach to the questions being addressed and has particular interests in the following areas:-

Angiogenesis. Angiogenesis, the growth of new blood vessels, is essential to the development of chronic inflammation and consequent tissue destruction. Inhibition of angiogenesis represents a novel strategy for treating chronic inflammation.

Apoptosis. Inflammatory cells can breakdown and release mediators that perpetuate the inflammatory response or they can undergo programmed cell death (apoptosis) during which cellular components are packaged into inert apoptotic bodies for removal by phagocytic cells. Induction of apoptosis in inflammatory cells may be a way of controlling excessive tissue damage during inflammation.

Inducible enzymes. Enzymes that give rise to inflammatory mediators, and are induced specifically at inflammatory sites, are attractive targets for antiinflammatory therapy as selective inhibitors should be relatively free of side effects.

PPARs. When activated, peroxisome proliferating activator receptors (PPARs) have the capability of inducing systems for metabolising, and therefore removing, lipid mediators of inflammation. Drugs designed to stimulate these receptors may represent a novel form of antiinflammatory therapy.

Stress proteins. These are induced when cells face stressful conditions and protect, for example, enzymes from becoming denatured and losing activity. Our data suggests that at least one of these proteins, heme oxygenase-1, may have a role in switching off the inflammatory response.

Tolerance induction: Many chronic inflammatory diseases are autoimmune in nature i.e. the mechanisms that normally lead to recognition and removal of infective agents turn against host tissues. The aim of this project is to switch off autoimmune processes by inducing a state of immunological tolerance to proteins endogenous to host tissues.

Many of these projects overlap and are encompassed by an overall philosophy of investigating how the body adapts to inflammatory stresses. In addition, many of these processes impact on other diseases for example tumour growth.