The environment in which we live is hostile. Evidence to support this statement includes the fact that, if skin is physically damaged, systemic infection by micro-organisms is quite likely to occur. Similarly, if the epithelium lining the intestine is damaged or functionally impaired, micro-organisms can enter the blood stream. For these reasons, peptic ulcer disease was, in the pre-antibiotic era, very much more dangerous than now.

Not all micro-organisms are harmful. Some multicellular animals, for example all ruminants, depend on the presence of commensal bacteria – bugs which normally inhabit the intestinal lumen and digest cellulose into products which are the nutrients for the "host" animal. It is perhaps not surprising that this situation has evolved, since bacteria have been around in such large numbers throughout mammalian evolution. If you consider that one gram of intestinal contents can contain up to one trillion bacteria, you can see how these barrier (epithelial) cells, which line the intestine and separate the body from the external environment, are integral to our health. It is a common misconception that we feed our gut when in actual fact it feeds us.

Certain micro-organisms are very harmful. The most common cause of death in children worldwide is dehydration due to intestinal infections with micro-organisms such as cholera, E. coli, campylobacter and salmonella, which are other common bacteria which evoke secretions leading to diarrhoea. Curiously, diarrhoea is a defensive response, designed to rid the host of these parasites. Tragically this is such a powerful mechanism that it can lead to fatal dehydration if water and electrolytes are not replaced.

Protective responses to harmful micro-organisms may be excessive or inappropriate. Inflammatory bowel disease (IBD) refers to a range of clinical conditions (e.g. Crohn’s disease and ulcerative colitis) which display similar symptoms that can range from mild intestinal disturbances to chronic diarrhoea and weight loss. Inflammation, a common feature of these diseases, is defined as how the immune system responds to injury. Ideally inflammation allows the body to heal damage that has occurred in response to a noxious stimulus. However, in IBD, non-resolving or uncontrolled inflammation is a feature. IBD is a young person’s disease, affecting a growing number of people.

Why does chronic inflammation occur? Causes of IBD are, as yet, unknown, with suspicion raised at everything from infection to diet. In addition, recent information strongly implicates a genetic component. However, what is clear is that the immune system is a major player in this disease. The majority of the time the immune system is a "good thing" and plays a crucial role in keeping us healthy. However, like most effective systems, the immune system can malfunction, with consequent collateral damage due to "friendly fire". In this case, the body’s immune system becomes out of control and turns on itself, damaging our own tissues and cells.

Science may help understand disease processes. Three main areas being investigated in our laboratory are:
i) How does the immune system function in the gut?
ii) Why does it malfunction in diseases like IBD?
iii) Can we develop new ways to interrupt or even prevent inflammatory disease processes?

For those who suffer from IBD, and their families, the last question may seem the most important. However, as scientists, we must recognise that it is only by understanding how a particular system works normally can we ever hope to discover why it fails and, therefore, how to stop this from happening.

So what does an immune reaction consist of? One of the most important events that occur is that immune cells respond to the stimulus (e.g. infection / autoimmune disease) by secreting chemical messengers or "mediators". These mediators are chemicals with which cells of the body communicate with each other. Designated cells of the immune system orchestrate this complex crosstalk. For example, locally released chemical mediators act on epithelial (barrier) cells lining the gut and stimulate water loss; the mechanism underlying diarrhoea. Another function of a specific sub-group of chemical mediators is to recruit immune cells from the blood to the site of infection to amplify protective responses to infection (or sustain an inappropriate or excessive inflammation). Thus cells will migrate toward sites of infection. Research carried out in many laboratories, including ours, focuses on trying to characterise these pro-inflammatory mediators which are so important in amplifying the immune response, as we consider these to be targets for novel anti-inflammatory drugs.

Figure 1: Crosstalk mechanisms involved in host response to micro-organisms.

Nature supplies "off" switches. Usually, wounds heal. Such resolution of damage is the ideal outcome of a disease process or response to injury. Thus, in addition to preventing synthesis or release of pro-inflammatory mediators, we can begin to consider amplification of normal curative processes. An opportunity has recently been identified by the discovery of a family of molecules which are anti-inflammatory - the lipoxins. Lipoxins are enormously powerful endogenous anti-inflammatory molecules which appear to limit or reverse inflammation as part of natural healing.