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Am J Physiol Endocrinol Metab (March 27, 2002). doi:10.1152/ajpendo.00426.2001
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Articles in PresS, published online ahead of print March 26, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00426.2001
Submitted on September 26, 2001
Accepted on March 18, 2002

Role of Cytokines and Testosterone in Regulating Lean Body Mass and Resting Energy Expenditure in HIV-Infected Men

Ronenn Roubenoff1*, Steven Grinspoon2, Paul R. Skolnik3, Eric Tchetgen3, Leslie Abad4, Donna Spiegelman5, Tamsin Knox3, and Sherwood Gorbach3

1 Department of Community Health and Department of Medicine, Tufts University School of Medicine, Boston, MA, USA; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
2 Division of Endocrinology, Massachusetts General Hospital, Boston, MA, USA
3 Department of Community Health and Department of Medicine, Tufts University School of Medicine, Boston, MA, USA
4 Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Department of Community Health and Department of Medicine, Tufts University School of Medicine, Boston, MA, USA
5 Department of Community Health and Department of Medicine, Tufts University School of Medicine, Boston, MA, USA; Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: roubenoff{at}hnrc.tufts.edu.

Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia (loss of lean body mass [LBM] without severe weight loss, often accompanied by elevated resting energy expenditure [REE]) is still common, and is driven by excessive production of the catabolic cytokines tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1ß (IL-1ß). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss > 1 kg occurred in 35% of the cohort and LBM loss > 5% occurred in 12.2% over 8 months of observation, but classical wasting (loss of =10% of weight) was rare (2%). Both TNF-{alpha} (-150 g LBM per ng mL-1, p < 0.02) and IL-1ß production (-130 g LBM per ng mL-1, p < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE > 200 kcal/d was found in 17.7% of the subjects, regardless of weight change. IL-1ß (+9 kcal/d per ng mL-1, p < 0.002) and TNF-{alpha} (+10 kcal/d per ng mL-1, p < 0.02) production predicted {Delta}REE. Serum free testosterone was inversely associated with TNF-{alpha} production, and was not an independent predictor of either {Delta}LBM or {Delta}REE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common, and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism.




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