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Tumor Necrosis Factor-a Production Is Associated with Less Body Cell Mass in Women with Rheumatoid Arthritis

JOSEPH WALSMITH, LESLIE ABAD, JOSEPH KEHAYIAS, and RONENN ROUBENOFF

ABSTRACT.

Objective.
To examine the relationship between inflammatory cytokine production and body cell mass (BCM) in women with stable, medically well-controlled rheumatoid arthritis (RA).

Methods. Case-control study of 20 women with RA and 20 healthy women matched for age, race, and body mass index (kg/m2). Tumor necrosis factor-a (TNF-a), interleukin 1ß (IL-1ß), and IL-6 production were measured by specific, non-cross-reacting ELISA of peripheral blood mononuclear cells (PBMC) cultured with and without 100 ng/ml of endotoxin. Total BCM was assessed by the reference method of whole-body counting of naturally occurring radioactive potassium-40.

Results. Patients with RA were cachectic, with 14% less BCM (p < 0.001) and higher TNF-a production (p < 0.05) than controls. TNF-a production was inversely associated with BCM both without (r = –0.51, p = 0.03) and with (r = –0.57, p = 0.01) endotoxin stimulation in patients but not in controls. In multivariate linear regression models, these inverse associations remained significant after adjustment for age and physical activity. No association was found for IL-1ß or IL-6 production in these models.

Conclusion. Women with stable, medically well-controlled RA have lower than normal BCM that is inversely associated with elevated TNF-a production. (J Rheumatol 2004;31:23-9)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
CACHEXIA
BODY CELL MASS
TUMOR NECROSIS FACTOR-a
WOMEN


From the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston; and the Division of Rheumatology/Immunology, Department of Medicine, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.

Supported by a Clinical Science Grant from the Arthritis Foundation, USDA Cooperative Agreement 58-1950-9-001, the Boston Obesity/Nutrition Research Center (grant P30-DK46200), and the National Center for Research Resources of the National Institute of Health M01 RR00054. J. Walsmith was supported by a National Research Service Award T32 AG00209-09.

J. Walsmith, MA, Doctoral Student, Tufts University; L. Abad, MS, Senior Research Technician; J. Kehayias, PhD, Chief, Body Composition Laboratory; R. Roubenoff, MD, MHS, Chief, Physiology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging and Associate Professor of Medicine and Nutrition.

The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Address reprint requests to Dr. R. Roubenoff, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: roubenoff@mpi.com

Submitted February 26, 2003; revision accepted June 25, 2003.




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