Low Body Cell Mass Linked to Elevated Tumour Necrosis Factor-Alpha in Women With Well-Controlled Rheumatoid Arthritis

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Low Body Cell Mass Linked to Elevated Tumour Necrosis Factor-Alpha in Women

With Well-Controlled Rheumatoid Arthritis

Journal of Rheumatology

01/16/2004

By Beth Nierengarten

Women with clinically controlled rheumatoid arthritis (RA) have lower then

normal body cell mass, which has now been found to correlate inversely with

elevated tumour necrosis factor (TNF)-alpha production.

Although it is known that cachexia contributes to increased morbidity and

early death in patients with RA, the mechanism by which cachexia develops in

RA patients is not clear, write ph Walsmith, MA, Tufts University, and

colleagues. Evidence suggests that the cytokines TNF-alpha and interleukin

1beta (IL-1beta) play major roles, but as yet there has been no evidence of

a direct association between these cytokines and depletion of body cell mass

in patients with well-controlled RA.

In their case-control study, Dr. Walsmith and colleagues compared cytokine

production and body cell mass in 20 women with clinically controlled RA

against a cohort of 20 healthy women matched for age, race and body mass

index (BMI). All RA patients had been free of disease flares for at least 3

months prior to study entry and had stable disease. Of the 20 RA patients, 9

were on prednisone, 9 on methotrexate, 6 on hydroxychloroquine and 15 on

nonsteroidal anti-inflammatory agents.

Peripheral blood mononuclear cells (PBMC) cultured with or without endotoxin

were used to measure production of TNF-alpha and IL-1beta.

Compared to healthy controls, RA patients had 14% less body cell mass (94.9%

vs. 81.7% g TBK, respectively; P < .001). After eliminating the 9

prednisone-treated patients from the analysis because of its possible

confounding effect, the remaining RA patients had 16% less body cell mass

than controls (79.8% vs. 94.9% g TBK, respectively; P < .001). No

significant difference in body cell mass was found between patients on

prednisone and controls.

Patients with RA had significantly higher production of PBMC-stimulated

TNF-alpha than controls (2722 vs. 1398 pg/mL, respectively; P < .05). No

significant difference between the two groups was found for PBMC-stimulated

IL-1beta.

In RA patients, an inverse relationship was found between body cell mass and

TNF-alpha production without endotoxin (P = .03) and with endotoxin (P =

..01) stimulation, but not in controls (P = .99 and P = .33, respectively).

After adjusting for age and physical activity, this inverse relationship

remained significant.

These data " strengthen the need to direct therapeutic interventions at

specific causes of rheumatoid cachexia, " conclude the authors, and that they

" reinforce the importance of investigating anti-cytokine therapy, and

specifically anti-TNF-alpha therapy, as a means of restoring body cell mass

in patients with RA. "

J Rheumatol 2004 Jan;31:1:23-9.