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Etanercept Reduces Number of Proinflammatory Cytokine-Secreting Peripheral Blood Mononuclear Cells in Patients with Rheumatoid Arthritis

Long-term treatment with etanercept in patients with rheumatoid arthritis (RA) appears to reduce the numbers of proinflammatory cytokine-secreting peripheral blood mononuclear cells (PBMC), while the number of IL-10-secreting cells is unaffected, perhaps accounting for the long-term systemic effects.

A significant proportion of patients fails to respond to etanercept. Both RA and etanercept influence cytokine levels; thus, the immunomodulatory effects of etanercept in vivo are of interest for predicting response and prognosis.

H. Schotte, MD, with the Universitatsklinikum Munster, in Germany, and colleagues determined the influence of etanercept treatment on the number of PBMC secreting immunoregulatory key cytokines and the correlation of these cell counts with treatment response in 19 patients with RA treated with etanercept monotherapy.

Frequencies of PBMC secreting cytokines were determined by ELISPOT analysis before and after 9 months of therapy and compared with values for healthy controls. The clinical outcome was assessed as defined by American College of Rheumatology (ACR) criteria.

Fifteen patients fulfilled ACR20, 7 fulfilled ACR50, and 2 fulfilled ACR70 criteria. Initially elevated levels of tumour necrosis factor-alpha- and interleukin (IL)-1beta-secreting PBMC were reduced compared to those of controls. In addition, normal or low numbers of IL-6- and interferon-gamma (IFN-gamma)-secreting PBMC were reduced below those of control levels.

The number of IL-10-secreting PBMC did not differ from that of healthy controls and did not change significantly over time. The pretreatment IFN-gamma:IL-10 ratio correlated to reduction in the tender and swollen joint counts.

"Our results provide evidence that long-term treatment with etanercept substantially down-regulates the activated systemic proinflammatory cytokine cascade in RA," Dr. Schotte and colleagues conclude. "The ratio of IFN-gamma:IL-10 secreting PBMC may serve as a prognostic parameter for the clinical response to etanercept treatment," they suggest.

Rheumatology (Oxford) 2004 Mar 16;[Epub ahead of print]. "Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis"

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