Drugs blocking the action of TNF ( Tumor Necrosis Factor ) have shown promise in the early treatment of rheumatoid arthritis.

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 researchers investigated the role of TNF in the conversion of biologically inactive DHEAS--dehydroepiandrosterone sulfate--to biologically active DHEA, the steroid hormone parent of androgen, estrogen, and testosterone.

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 rheumatoid arthritis, with disease duration averaging 15 years. 22 of the patients were osteoarthritis 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 rheumatoid arthritis and osteoarthritis patients.

On the evidence of both synovial cell and synovial fluid analysis, levels of DHEA from DHEAS were significantly lower among rheumatoid arthritis patients than osteoarthritis patients. In addition, researchers found a negative correlation between converted DHEA and markers of inflammation among rheumatoid arthritis patients but not in patients with osteoarthritis. 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 rheumatoid arthritis as compared with that in patients with osteoarthritis," notes leading contributor Claudia 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 rheumatoid arthritis but absolutely not in patients with osteoarthritis."

Providing the full picture of androgen deficiency in rheumatoid arthritis, this study affirms the need for further research into early anti-TNF antibody therapy in the treatment of this particular inflammatory disease.

Source: Arthritis & Rheumatism, 2005


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