Therapeutic implications for interferon-alpha in arthritis: a pilot study.
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.


CONCLUSIONS
These in vitro data suggest a therapeutic role for IFN-a in the treatment of arthritis through upregulation of critical cytokine antagonists.
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Thomas
T
Wong
Beata
B
Majchrzak
Earl
E
Bogoch
Edward C
EC
Keystone
Eleanor N
EN
Fish
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D000068800:Etanercept; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D008562:Membrane Glycoproteins / Q000235:genetics; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology; D053244:Osteoprotegerin; D010865:Pilot Projects; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D013582:Synovial Fluid / Q000166:cytology; D013583:Synovial Membrane / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
D002352:Carrier Proteins; D006023:Glycoproteins; C507763:IL1RN protein, human; D007074:Immunoglobulin G; D007155:Immunologic Factors; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000068800:Etanercept