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Abnormal Regulation of Interleukin 6 in Systemic Juvenile Idiopathic Arthritis

PATRIZIA PIGNATTI, MARINA VIVARELLI, CRISTINA MEAZZA, MARIA GRAZIA RIZZOLO, ALBERTO MARTINI, and FABRIZIO DE BENEDETTI

ABSTRACT.

Objective.
To evaluate the in vitro production of interleukin 6 (IL-6) by peripheral blood mononuclear cells (PBMC) of patients with systemic juvenile idiopathic arthritis (JIA), its regulation by IL-10, and the association of abnormal regulation of IL-6 production with presence of polymorphisms in the regulatory sequence of the IL-6 gene.

Methods. PBMC were cultured in the absence or presence of lipopolysaccharide (LPS). IL-6 and IL-10 levels were measured by ELISA. Polymorphisms in the regulatory sequences of the IL-6 gene were assessed by restriction fragment length polymorphism analysis and sequencing of amplified regions.

Results. Patients' PBMC produced high amounts of IL-6 compared to controls in unstimulated conditions. The IL-10 50% inhibitory dose of LPS stimulated IL-6 production was significantly higher in patients than controls. IL-10 levels produced in the absence or presence of LPS were comparable between patients and controls. The -174 G/C polymorphism in the IL-6 gene does not appear to be correlated with the high unstimulated IL-6 production or with the reduced inhibition by IL-10 observed in patients with JIA. No differences in patients compared to controls and with respect to the published sequence were found in the 3' untranslated region (UTR) of the IL-6 gene.

Conclusion. Most patients with JIA have increased unstimulated production of IL-6 and reduced inhibition of IL-6 production by IL-10. This abnormal regulation of IL-6 production is not secondary to a defect in IL-10 production, and is not associated with polymorphism of alleles at position -174 of the 5' flanking region or with mutations in the 3' untranslated region of the IL-6 gene. (J Rheumatol 2001;28:1670-6)

Key Indexing Terms:

INTERLEUKIN 6
INTERLEUKIN 10
POLYMORPHISM
JUVENILE IDIOPATHIC ARTHRITIS



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