Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation.

OBJECTIVE

Several clinical studies performed with human recombinant interleukin 10 (IL-10) in patients with rheumatoid arthritis (RA) have shown little efficacy. We investigated potentially proinflammatory in vivo effects of IL-10 in humans. We evaluated the upregulation of Fc gamma receptor (Fc gamma R) expression on monocytes/macrophages (and granulocytes) in patients with RA receiving different dosages of IL-10.

METHODS

Together with changes in disease activity and several cell markers, the expression of Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII was determined on granulocytes and monocytes/macrophages from the peripheral blood of 6 patients with active RA before and after treatment with recombinant human IL-10. In addition, the in vitro effect of IL-10 on Fc gamma R expression on monocytes/macrophages in combination with their susceptibility to immune complex induced production of tumor necrosis factor-alpha(TNF-alpha) was assessed.

RESULTS

Clinical improvement was not observed in the IL-10 treated patients (based on ACR20 criteria). Significant decreases in thrombocyte numbers were observed in patients receiving IL-10. No changes in cell markers such as CD14 were found. On the other hand, expression of Fc gamma RI and Fc gamma RIIa on monocytes/macrophages was increased upon high dose IL-10 treatment. Interestingly, increases in expression of Fc gamma RI and Fc gamma RIIa correlated with a decrease in thrombocyte numbers. In vitro, IL-10 similarly upregulated Fc gamma RI and Fc gamma RIIa expression on monocytes/macrophages from RA patients. This was accompanied by increased TNF-a production after immune complex stimulation.

CONCLUSION

These findings indicate that upregulation of Fc gamma R expression in RA with IL-10 treatment may counteract the otherwise antiinflammatory effects of IL-10 by potentiating immune complex mediated proinflammatory responses.