Bulking Up the Immune System: Growth hormone rejuvenates bone marrow, thymus (Immunology)

Abstract

Growth hormone (GH) hardens muscles and purges fat, which explains its illicit appeal for athletes trying to improve their performance and old folks hoping to retain their muscle tone. New research suggests that GH is also vital for keeping the immune system fit. Treating old rats with GH rebuilds the populations of hematopoietic cells that give rise to new red and white blood cells, a finding that suggests one strategy for bolstering the faltering immune systems of the elderly. Our GH levels peak in infancy. Their decline in middle and old age causes a decrease in muscle size and strength, and accumulation of fat. At the same time that we're developing love handles, pot bellies, and cottage cheese thighs, our immune systems are flagging. The parallel declines in GH and immune function are not coincidental. Fifteen years ago, for instance, Keith Kelley of the University of Illinois, Urbana-Champaign, and colleagues showed that GH implants could revitalize the thymus--the gland in the neck where T cells mature--in aged rats. To find out whether GH has a similar effect on the bone marrow, French and colleagues implanted GH-releasing rat pituitary cells into one group of grizzled, 2-year-old rats and injected a second group of oldsters twice a day for a month with the human form of the hormone that had been produced in bacteria. For the immune system, this GH jolt proved to be a tonic. In both groups, the number of hematopoietic cells in the bone marrow zoomed to nearly the same level as in young rats. For example, the animals that received implants boasted more than three times the number of hematopoietic cells as did untreated elderly rats. GH sparked other changes in the bone marrow. As we age, fat not only sprawls over the hips and belly, it also piles up inside the bones, replacing hematopoietic cells. But the leg bones of GH-treated rats contained only slightly more fat cells than did the bones of the young rats. The thymus also rebounded to its youthful structure of distinct inner and outer layers that house adolescent T cells. How GH revives the bone marrow remains uncertain. The hormone might directly protect the hematopoietic cells. But Kelley favors a second possibility: that GH acts indirectly by triggering the release of another hormone, insulin-like growth factor-1 (IGF-1). IGF-1 exerts widespread effects on growth and metabolism, and Kelley thinks it might prevent the bone marrow cells from dying off as the animals age. On the surface, the results might seem perplexing, given suggestions that GH and IGF-1 speed death in mice (see "Growing Old Together" ), says William Sonntag, a neuroendocrinologist at Wake Forest University in Winston-Salem, North Carolina. However, immune system function doesn't necessarily correlate with life-span. Other studies have shown that GH revs up the aging immune system. "This [work] fits exactly with what we expect growth hormone to do," he says. GH is no panacea--prolonged use can cause carpal tunnel syndrome and might promote cancer (see "Strong Muscles, Strong Tumors?" )--but Sonntag thinks the results warrant starting short-term clinical trials. Kelley agrees that the time is right for trials of GH as an immune booster for the elderly: "This stuff is ready to go." --Mitch Leslie; suggested by Jennifer Fuller R. A. French, S. R. Broussard, W. A. Meier, C. Minshall, S. Arkins, J. F. Zachary, R. Dantzer, K. W. Kelley, Age-associated loss of bone marrow hematopoietic cells is reversed by GH and accompanies thymic reconstitution. Endocrinology 143 , 690-699 (2002). [Abstract] [Full Text]