Brain leptin receptors in inflammation

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Communication between the immune system and the brain is important for our ability to respond to and mount an effective defense response against invading pathogens. Products of the peripheral immune system, known as cytokines (eg. Interleukin-1), play an important role in this communication. These molecules can enter the brain from the circulation and can actually be produced by brain cells following a systemic inflammatory or infectious signal. In the brain, cytokines act to trigger a number of 'sickness' responses such as fever, appetite suppression and increased sleep.  We have previously shown that a new member of this family, leptin, which is involved in the physiological control of body weight, stimulates the production of cytokines in the brain and may act as a circulating messenger during disease. Under normal conditions, the main function of leptin is to regulate our appetite, however we have previously demonstrated that in addition to this, it can induce fever, which is a hallmark of disease. More recently we have demonstrated that this effect of leptin is linked to the body's defense mechanisms against bacterial infection and inflammation. These discoveries led us to suggest that the different actions of leptin in the brain ie appetite suppression and fever, are controlled by different brain sites. We now intend to identify these different brain targets and investigate the mechanisms of action of this hormone in disease.