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HIGHLY ELEVATED LEVELS OF SERUM INTERLEUKIN-18 IN ADULT ONSET STILL'S DISEASE

M. Kawashima, M. Yamamura, Y. Morita, T. Tanimoto1, M. Kurimoto1, H. Makino

Department of Medicine III, Okayama University Medical School, Okayama 700-8558, 1Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama 702-8006, Japan


Objective: Adult onset Still's disease (AOSD) is a form of polyarthritis associated with systemic manifestations such as high spike fever, sore throat, and an evanescent erythematous salmon-colored rash, and is occasionally complicated by various organ failures. The levels of interleukin-18, a recently identified inflammatory cytokine, in the blood circulation of AOSD was determined.


Methods: Serum samples were obtained from patients with AOSD, rheumatoid arthritis (RA), systemic lupus arthritis (SLE), polymyositis/dermatomyositis (PM/DM), or systemic sclerosis (SSc), or from healthy controls (HC), and their IL-18 levels were measured by a sandwich ELISA. The presence of biological active IL-18 in serum from active AOSD patients were examined by using IL-18-resposive human myelomonocyte cell-lines (KG-1 cells). In addition, serum levels of inflammatory cytokines such as IL-1b, TNF-a, IL-6, and M-CSF were measured by ELISA.


Results: The mean (▒ SD) values of circulating IL-18 were markedly greater in active AOSD patients (n = 14; 80700 ▒ 105100 pg/ml) as compared with patients with either RA (n = 20; 297 ▒ 211 pg/ml), SLE (n = 19; 266 ▒ 113 pg/ml), PM/DM (n = 12; 146 ▒ 44 pg/ml), or SSc (n = 13; 161 ▒ 97 pg/ml), or HC (n = 30; 157 ▒ 69 pg/ml). Serum samples of AOSD patients could stimulate IFN-g production by KG-1 cells, and this activity was blocked by IL-18-specific antibodies; however, their biologically activities of IL-18 were much lower than estimated by ELISA (n = 4; 90 ▒ 74 pg/ml). IL-1b, TNF-a, IL-6, and M-CSF were detectable in serum of AOSD, but these cytokine levels were almost comparable to those of RA. Finally, IL-18 levels were found to be immediately decreased following corticosteroid therapy and correlate with levels of serum ferritin in AOSD patients


Conclusion: These data indicate that IL-18 is circulating at significantly high levels in AOSD patients, in association with their disease activity.

Disclosure: work reported in this abstract was supported by:
Personal funds.

Abstract: 42
November 9, 1998
Poster Session A: Cytokines I
8:00-9:30 am, Hall B1/C



Interferons
Interleukins: other
Rheumatologic disorders: other
Steroids

 

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