Sci. Aging Knowl. Environ., 14 July 2004
Vol. 2004, Issue 28, p. nf65
[DOI: 10.1126/sageke.2004.28.nf65]


Opposites Detract

Hunger hormone quenches inflammation, opposing leptin

Mitch Leslie

Sherlock Holmes had Professor Moriarty. Magic Johnson had Larry Bird. Britney Spears has Christina Aguilera. A less famous rivalry occurs in the body, pitting the weight-regulating hormones leptin and ghrelin against each other. The molecules not only exert opposite effects on appetite, but new research suggests that they trigger contrasting reactions from the immune system. The discovery might help researchers develop treatments that soothe diseases that can stem from inflammation, including diabetes and atherosclerosis.

Ghrelin makes us want to eat, whereas leptin squelches hunger. Paradoxically, obese people usually produce too little ghrelin and an oversupply of leptin. Excess weight also promotes atherosclerosis, diabetes, and other illnesses, and many researchers suspect that inflammation underlies many of these conditions. Obese patients carry large quantities of cytokines, or chemical messengers, that spark inflammation. Because leptin prods immune cells to pour out these molecules, the hormone might help cause obesity-related inflammation. Immunologist Dennis Taub of the National Institute on Aging branch in Baltimore, Maryland, and colleagues wanted to find out whether ghrelin too adjusts the immune system.

The researchers first determined whether ghrelin affects immune cells. They found that T cells bear the receptor protein for the hormone. Stimulating the receptor hiked the amounts of calcium within the cells, indicating that they'd responded to ghrelin. Moreover, T cells also produce and emit ghrelin, the scientists found. These observations suggest that the hormone serves as an immune signal. Next, the team prodded immune cells with a compound that stimulates them to spill cytokines. Adding ghrelin slashed the output of most cytokines, and combining ghrelin with a molecule that blocks its receptor prevented this decline. The researchers then dosed T cells with ghrelin and leptin or with leptin alone. The single hormone provoked a surge of cytokines, which the mixture curtailed. "It's almost as if ghrelin is made to bring everything back to equilibrium," says Taub. That capability might allow ghrelin to ease autoimmune diseases such as rheumatoid arthritis and multiple sclerosis and to pacify the inflammation that can provoke diabetes and heart disease, he says. Besides inflammation, old age and autoimmune diseases often involve reduced appetite, and ghrelin might help both problems, he adds.

"I think it's very exciting," says cardiologist Neal Weintraub of the University of Iowa College of Medicine in Iowa City. Two months ago, he and his colleagues reported that ghrelin stanches cytokine release by blood vessel cells. The new work shows that it can also exert the same effect on immune cells, he says. Although defenses against infection don't seem like a luxury, the ability to adjust them would benefit organisms evolutionarily, says endocrinologist David Cummings of the University of Washington School of Medicine in Seattle. "The immune system is expensive to run, and it makes sense to shut it down" during periods of food scarcity, he says. But even in times of plenty, ghrelin's ability to tweak the immune system might help tame runaway inflammation. In the rivalry between leptin and ghrelin, this work might win ghrelin some fans.

July 14, 2004
  1. V. D. Dixit et al., Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 114, 57-66 (2004). [CrossRef][Medline]
  2. W. G. Li et al., Ghrelin inhibits proinflammatory responses and nuclear factor-{kappa}B activation in human endothelial cells. Circulation 109, 2221-2226 (2004). [Abstract/Free Full Text]
Citation: M. Leslie, Opposites Detract. Sci. Aging Knowl. Environ. 2004 (28), nf65 (2004).

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