Sick of hunger

By Michael Day MILLIONS of malnourished people in the developing world are magnets for infectious disease because levels of a hormone called leptin fall to low levels, immunologists suggested this week. If they are right, the finding could lead to a rethink of how to help save the lives of starving populations. Experts have greeted the suggestion with optimism. “There are 180 million malnourished children in the world. That’s three times the child population of the United States,” says Lawrence Haddad of the International Food Policy Research Institute in Washington DC. “So any development that could help their immune systems would be tremendous.” Malnutrition plays a role in the deaths of more than 6 million people, mostly children, each year. For decades, experts have known that starvation diets cause weakened immunity. This could help explain why diseases such as measles and pneumonia kill so many children in developing countries. Lack of minerals and vitamins in diets has taken some of the blame. But exactly why starvation makes people susceptible to infectious diseases has been unclear. Graham Lord and his colleagues at Imperial College’s school of medicine in London believe they have now found a large part of the answer—the hormone leptin, which regulates appetite. Researchers have already seen low leptin levels in people who are underweight, and starved mice. To find out more about the effects of low leptin levels, the Imperial College team incubated human CD4 cells—cells that orchestrate the immune response—with other cells that can provoke an immune response in which the CD4 cells multiply. They say that adding leptin in various concentrations had a striking effect (Nature, vol 394, p 897). The more concentrated the leptin, the higher the number of CD4 cells. The team then tested the result in controlled experiments with mice. They starved 24 mice for 28 hours, which lowered their leptin levels. This led to a 69 per cent reduction in the animal’s immune response to the chemical oxazolone, which causes inflammation. But twice-daily injections of leptin during starvation prevented the immune suppression. Lord says that giving leptin to malnourished children at the same time as vaccinations, for measles for example, may make immunisation more effective. “It seems that by keeping leptin levels up we’re telling the body to keep immune function up,” Lord told New Scientist. “But below a certain level, leptin switches off or diverts energy expenditure from non-vital functions including the immune system to things like the brain and the heart.” However, the results are surprising from an evolutionary perspective, says immunologist Doug Fearon of Cambridge University. “You’d have to count the cell-mediated immune system as a fairly vital system,” he says. He doubts that the immune system uses much energy, even when gearing up to fight a new infection, so giving up that energy to organs such as the heart would seem counterproductive. However, “that doesn’t make what they observed any less interesting”, Fearon says. “This study provides a fascinating explanation for the link between nutritional status and reduced immune responsiveness,” adds Paul Trayhurn of the Rowett Research Institute in Aberdeen. He believes it adds support to the idea that leptin’s primary purpose is to “signal starvation”. Lord notes that other people with depressed immunity, such as patients with HIV,
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