Interleukin 10 Treatment of Patients with Rheumatoid Arthritis Enhances Fcg Receptor Expression on Monocytes and Responsiveness to Immune Complex Stimulation

JOEL A.G. VAN ROON, SISKA WIJNGAARDEN, FLORIS P.J.G. LAFEBER, CORA DAMEN, JAN G.J. VAN DE WINKEL, and JOHANNES W.J. BIJLSMA

ABSTRACT.

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 Fcg receptor (FcgR) 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 FcgRI, FcgRIIa, and FcgRIII 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 FcgR expression on monocytes/macrophages in combination with their susceptibility to immune complex induced production of tumor necrosis factor-a (TNF-a) 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 FcgRI and FcgRIIa on monocytes/macrophages was increased upon high dose IL-10 treatment. Interestingly, increases in expression of FcgRI and FcgRIIa correlated with a decrease in thrombocyte numbers. In vitro, IL-10 similarly upregulated FcgRI and FcgRIIa 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 FcgR expression in RA with IL-10 treatment may counteract the otherwise antiinflammatory effects of IL-10 by potentiating immune complex mediated proinflammatory responses. (J Rheumatol 2003;30:648-51)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
CLINICAL TRIAL
INTERLEUKIN 10
Fcg RECEPTORS
IMMUNE COMPLEXES
TUMOR NECROSIS FACTOR-a

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From the Departments of Immunology and Rheumatology and Clinical Immunology, University Medical Centre Utrecht, and Genmab, Utrecht, The Netherlands.

Supported by the Nationaal Reumafonds (The Dutch League against Rheumatism).

J.A.G. van Roon, PhD; S. Wijngaarden, MD; F.P.J.G. Lafeber, PhD; J.W.J. Bijlsma, MD, Professor, Department of Rheumatology and Clinical Immunology, UMC Utrecht; C. Damen, Technician; J.G.J. van de Winkel, Professor, Department of Immunology, UMC Utrecht, and Genmab.

Address reprint requests to Dr. J.A.G. van Roon, Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. E-mail: J.vanRoon@azu.nl

Submitted April 5, 2002; revision accepted October 21, 2002.

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