Metabolomics in the Analysis of Inflammatory Diseases

Inflammation is a normal and extraordinarily important component of responses to infection and injury. The cardinal features of swelling, redness, stiffness and increasing temperature are strong indicators of the significant changes in tissue metabolism and the ingress of immune cells into the tissues. The increase in blood flow which underlies many of these changes may result in changes to the supply of nutrients and in particular the level of oxygen in the tissues. Inward migration of immune cells, which is also enabled by the increased blood flow, will put further stress on the metabolic environment of the tissues. The activity of macrophages and neutrophils in clearing infection and repairing tissue damage also have significant metabolic consequences particularly because of the production of cytokines and cytotoxic molecules such as reactive oxygen species and reactive nitrogen species, which are required to kill invading organisms. Production of these molecules will consume considerable quantities of oxygen, ATP and NADPH. These antimicrobial agents put considerable stress on host cells in the surrounding and distal tissues and can lead to significant loss of protective metabolites such as glutathione. Most infections and traumatic injuries are cleared or repaired relatively rapidly and metabolic homoeostasis is soon restored. However, there is a broad range of inflammatory diseases which involve chronic activation of the immune system and, as a result, chronic persistent inflammation. We have been studying the metabolic consequences of chronic inflammatory diseases with the aim of identifying metabolic fingerprints which may provide clues about why the localised tissue disease persists. For example, why in rheumatoid arthritis does persistent inflammation lead to widespread cartilage and joint destruction? However, the metabolic consequences of chronic inflammation are much more widespread than the localised disease and can lead on to important comorbidities such as accelerated atherosclerosis and cardiovascular disease. Metabolomic analysis may be able to distinguish between localised and systemic metabolic consequences of inflammation and provide novel targets for therapeutic intervention in these important human diseases.