Therapeutic Implications for Interferon-a in Arthritis: A Pilot Study

THOMAS WONG, BEATA MAJCHRZAK, EARL BOGOCH, EDWARD C. KEYSTONE, and ELEANOR N. FISH

ABSTRACT.

Objective. To evaluate the therapeutic potential of interferon-a (IFN-a) in osteoarthritis (OA) and rheumatoid arthritis (RA) by examining regulation of cytokine antagonist expression.

Methods. Expression of interleukin 1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor (sTNFR) was examined by ELISA in cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with OA or RA, either left untreated or treated with IFN-a. Single (7) and paired (5) SF and ST cells from OA and RA patients were examined. As well, the ability of IFN-a to regulate gene expression levels for osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) was examined in freshly isolated SF cells from patients with RA, by reverse transcriptase polymerase chain reaction.

Results. IL-1Ra and sTNFR were found to be constitutively expressed in OA and RA SF and ST cells. IFN-a treatment resulted in an increase in both IL 1Ra and sTNFR production. Freshly isolated RA SF cells exhibited constitutive OPGL gene expression in both the non-T and T cell fractions of the SF. In contrast, OPG gene expression levels were undetectable or low. IFN-a treatment of RA SF cells resulted in upregulation of OPG gene expression in the T cell fraction of the RA SF cells, whereas OPGL gene expression remained unaffected.

Conclusion. These in vitro data suggest a therapeutic role for IFN-a in the treatment of arthritis through upregulation of critical cytokine antagonists. (J Rheumatol 2003;30:934-40)

Key Indexing Terms:

OSTEOARTHRITIS
RHEUMATOID ARTHRITIS
INTERFERON-a
SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR
OSTEOPROTEGERIN
OSTEOPROTEGERIN LIGAND
INTERLEUKIN 1 RECEPTOR ANTAGONIST

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From the Toronto General Research Institute, University Health Network; Department of Immunology, University of Toronto; Division of Rheumatology, St. Michael's Hospital; and Division of Advanced Therapeutics, Mount Sinai Hospital, Toronto, Ontario, Canada.

Supported by a grant from The Arthritis Society to Dr. E. Fish.

T. Wong, BSc; B. Majchrzak, MSc, Toronto General Research Institute; E. Bogoch, MD, Division of Rheumatology, St. Michael's Hospital; E.C. Keystone, MD, Division of Advanced Therapeutics, Mount Sinai Hospital; E.N. Fish, PhD, Toronto General Research Institute, Department of Immunology, University of Toronto.

Address reprint requests to Dr. E.N. Fish, Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 67 College Street, Room 424, Toronto, Ontario M5G 2M1, Canada.

Submitted April 29, 2002; revision accepted October 21, 2002.

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