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Detection of Interleukin 1ß (IL-1ß), IL-6, and Tumor Necrosis Factor-a in Skin of Patients with Fibromyalgia

SOUZAN SALEMI, JANINE RETHAGE, UWE WOLLINA, BEAT A. MICHEL, RENATE E. GAY, STEFFEN GAY, and HAIKO SPROTT

ABSTRACT.

Objective.
To determine if abnormal collagen metabolism is correlated with neurogenic inflammation, a potential activator of collagen metabolism, in patients with fibromyalgia (FM).

Methods. The presence of inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-a was investigated in skin tissues by using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifty-three skin biopsies from female patients with FM (30-65 years of age) were examined and compared to skin biopsies of 10 age and sex matched healthy controls. Biopsies were obtained from the left deltoid region. Rheumatoid arthritis synovial fibroblasts and tissues were used as positive controls for the expression of cytokines. Total RNA isolated from the tissue samples were reverse transcribed (RT) by random hexamers as the primer for RT followed by PCR amplification using specific primers for IL-1ß, IL-6 or TNF-a. Expression of IL-1ß, and TNF-a protein was investigated in the skin by immunohistochemistry using specific antibodies (avidin-biotin method).

Results. Positive signals (RT-PCR) were detected in skin tissues of 19/50 (38%) FM patients for IL-1ß, in 14/51 FM patients (27%) for IL-6, and in 17/53 patients (32%) for TNF-a. None of the cytokines could be detected in healthy control skin. Immunoreactivity for IL-1ß and TNF-a was demonstrated in certain skin tissues of our FM patients.

Conclusion. The detection of cytokines in FM skin indicates the presence of inflammatory foci (neurogenic inflammation) in the skin of certain patients (about 30% of FM patients), suggesting an inflammatory component in the induction of pain. This may explain the response to nonsteroidal antiinflammatory therapy in a subset of FM patients. (J Rheumatol 2003;30:146-50)

Key Indexing Terms:

FIBROMYALGIA
CYTOKINES
INTERLEUKINS
TUMOR NECROSIS FACTOR
SKIN


From the Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Zürich, Switzerland and the Department of Dermatology Allergology, Friedrich-Schiller University, Jena, Germany.

Supported in part by the Zurzach foundation, the American Fibromyalgia Syndrome Association (AFSA), and the Albert Böni Foundation.

S. Salemi, PhD; J. Rethage, Msc; B.A. Michel, MD; R.E. Gay, MD; S. Gay, MD, H. Sprott, MD, Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital; U. Wollina, MD, Department of Dermatology and Allergology, Friedrich-Schiller University.

Address reprint requests to Dr. H. Sprott, Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, CH-8091 Zürich, Switzerland. E-mail: haiko.sprott@ruz.usz.ch

Submitted March 18, 2002; revision accepted May 24, 2002.




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