New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone Production In Rheumatoid Arthritis

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New Insights Into Role Of Tumor Necrosis Factor On Sex Hormone

Production In Rheumatoid Arthritis

A protein involved in multiple cell functions, tumor necrosis factor

(TNF) is perhaps best known for provoking destructive inflammation.

Recently, drugs blocking the action of TNF have shown promise in the

early treatment of rheumatoid arthritis (RA).

To expand the understanding of TNF's function in chronic inflammatory

diseases, researchers at University Hospital Regensburg in Germany and

the National Institute of Rheumatic Diseases in the Slovak Republic

decided to take a closer look at this cytokine's impact on androgen

production. Androgens are thought to play a critical anti-inflammatory

role in rheumatic diseases, including various forms of arthritis and

lupus, based on extensive clinical trials and animal models. For their

study, the team investigated the role of TNF in the conversion of

biologically inactive DHEAS--short for dehydroepiandrosterone

sulfate--to biologically active DHEA, the steroid hormone parent of

androgen, estrogen, and testosterone. Their findings, featured in the

June 2005 issue of Arthritis & Rheumatism

(http://www.interscience.wiley.com/journal/arthritis), shed new light

on suppression of androgen by TNF in RA patients, as well as on the

different nature of inflammation in RA from the most common

inflammatory disease: osteoarthritis (OA).

To get a clear picture of how TNF affects hormone production and

regulation, the research team analyzed samples of inflamed synovial

tissue--obtained immediately after opening the knee joint capsules of

37 patients who underwent elective joint replacement surgery. 15 of the

patients had a longstanding history of RA, with disease duration

averaging 15 years. 22 of the patients were OA sufferers. Using tools

for biochemical analysis, the team assessed the process of converting

DHEAS to DHEA. The results revealed marked differences in the cellular

activity of RA and OA patients.

On the evidence of both synovial cell and synovial fluid analysis,

levels of DHEA from DHEAS were significantly lower among RA patients

than OA patients. In addition, researchers found a negative correlation

between converted DHEA and markers of inflammation among RA patients

but not in patients with OA. They also found evidence that TNF inhibits

the activity of steroid sulfatase, the key enzyme in DHEAS-to-DHEA

conversion.

" This is the first study to demonstrate that the conversion of DHEAS to

DHEA is decreased in patients with RA as compared with that in patients

with OA, " notes leading contributor Weidler. " In the present

study, we were fortunate to demonstrate that TNF is also a strong

inhibitor of the conversion of DHEAS to DHEA in synovial cells from

patients with RA but absolutely not in patients with OA. "

Providing the full picture of androgen deficiency in RA, this study

affirms the need for further research into early anti-TNF antibody

therapy in the treatment of this particular inflammatory disease.

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Article: " Tumor Necrosis Factor Inhibits Conversion of

Dehydroepiandrosterone (DHEAS) TO DHEA in Rheumatoid Arthritis Synovial

Cells: A Prerequisite for Local Androgen Deficiency, " Weidler,

Sona Struharova, Schmidt, Bernhard Ugele, Jürgen Schölmerich,

and Rainer H. Straub, Arthritis & Rheumatism, June 2005; 52:6; pp.

1721-1729.