Sjögren's Syndrome with Myalgia Is Associated with Subnormal Secretion of Cytokines by Peripheral Blood Mononuclear Cells

PER ERIKSSON, CARINA ANDERSSON, CHRISTINA EKERFELT, JAN ERNERUDH, and THOMAS SKOGH

ABSTRACT.

Objective. To measure in vitro cytokine release from peripheral blood mononuclear cells (PBMC) and serum cytokines in patients with primary Sjögren's syndrome (SS) with and without myalgia, compared to patients with rheumatoid arthritis (RA) and healthy controls.

Methods. Sixteen women with SS (8 with myalgia, 8 without pain), 15 women with RA, and 14 healthy women were studied. PBMC were isolated and cultured. Secretion of interleukin 1ß (IL-1ß), IL-6, IL-10, and tumor necrosis factor-a (TNF-a) was measured in cell supernatants with or without stimulation with phytohemagglutinin, tetanus toxoid, or purified protein derivative (PPD). Enzyme-linked immunospot was used to enumerate interferon-g (IFN-g) and IL-4-secreting cells. Serum concentrations of IL-8 and IL-18 were analyzed by ELISA.

Results. PPD-stimulated PBMC from SS patients responded with less production of IL-10, TNF-a, and IFN-g compared to controls. Patients with SS and pain were hyporesponsive also with respect to IL-1ß and IL-6. The generally subnormal cytokine release was statistically significant in myalgic patients with SS compared to healthy controls. Serum IL-18 was increased in both SS groups as well as in patients with RA, and the highest levels were found in myalgic patients with SS. Serum IL-8 was increased in RA but not in SS.

Conclusion. Patients with SS, especially those with myalgia, had diminished PBMC cytokine release and increased serum IL-18. This finding suggests that impaired cytokine regulation may have pathogenetic importance for myalgia in SS. (J Rheumatol 2004;31:729-35)

Key Indexing Terms:

PRIMARY SJÖGREN'S SYNDROME
CYTOKINES
INTERLEUKIN 18
MYALGIA

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From the Division of Rheumatology and Division of Clinical Immunology, Department of Molecular and Clinical Medicine, Autoimmunity and Immunoregulation Unit (AIR), Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.

Supported by the County Council of Östergötland, the Swedish Rheumatism Association, the Swedish Research Council (project number K-2003-74VX-14594-OIA), Siv Olsson's Foundation, and Karin Svensson's Foundation.

P. Eriksson, MD, PhD, Consultant Physician; C. Andersson, Laboratory Technician; T. Skogh, MD, PhD, Professor, Consultant Physician, Division of Rheumatology; C. Ekerfelt, PhD, Senior Lecturer; J. Ernerudh, MD, PhD, Professor, Consultant Physician, Division of Clinical Immunology.

Address reprint requests to Dr. P. Eriksson, Division of Rheumatology, Linköping University Hospital, SE-581 85 Linköping, Sweden. E-mail: per.eriksson@lio.se

Submitted May 20, 2003; revision accepted September 30, 2003.

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