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Starving the immune system

Malnutrition can kill, but often the cause of death is an infectious disease rather than a direct lack of nutrients. The susceptibility to infection in people with low body weight is linked to a suppressed immune system, but it was never clear how. A report in the 27 August 1998 issue of Nature now describes why starvation diets have such a detrimental effect on the immune system.

There has been a lot of progress in recent years in understanding the hormonal and genetic controls of obesity. One important finding was a gene in mice whose deficiency led to obesity. The gene, subsequently named obese, was later found to produce a hormone known as leptin. Leptin seems to suppress appetite, and without it the mice simply overeat.

One other, rather overlooked, problem in mice with faulty obese genes was a certain impairment in the immune system. People with low body weight have the same impairment. It is perhaps not surprising that people researching malnutrition failed to spot this important clue from studies of obesity.

Only now have Robert Lechler and his colleagues from the Hammersmith Hospital in London, UK, linked the two symptoms. Low leptin levels - which can be the result of a faulty obese gene or of malnutrition - seem to account for the observed immune suppression.

Most leptin is manufactured and secreted by fat-storing cells beneath the skin. The hormone circulates in the blood, and allows the brain to keep tabs on how much fat is being stored. The more stored fat cells there are, the higher the levels of leptin, and the more appetite suppression.

The system is more complex than this, or we would stay exactly the same weight, but the long-term aim is to maintain a consistent fat store. Leptin is also produced by the stomach, so it may regulate appetite in response to eating, in a much more immediate way. But when animals or people are malnourished, the levels of this hormone circulating in the blood drop, as expected when there are fewer fat-storage cells.

But as well as controlling appetite, the researchers find that leptin seems to be important in modulating certain parts of the immune system. The hormone promotes the proliferation of one class of T-cell - a type of white blood cell found in lymph nodes, the spleen and the blood, which become activated by foreign antigens. Leptin also increases the number of white blood cells circulating in the blood.

Another influence of leptin was to alter the secretion of signal chemicals produced by the immune cells to stimulate further immune activity. Leptin seemed to cause a bias in the production of T-cells which secrete the signals to set off the defensive inflammatory responses. A continuing chain of signals and immune system recruitment follows treatment with leptin.

Just 48 hours without food can have a severe effect on the immune system of mice. But treating mice with leptin protects them from starvation-induced immunodeficiency.

The researchers say that their findings show that leptin is the link between nutritional status and the effectiveness of our immune system. It explains why so many people who are malnourished are susceptible to infectious disease.

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Phillips, H. Starving the immune system. Nature (1998). https://doi.org/10.1038/news980903-2

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