Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis

• Published in: Journal of rheumatology 2001-07, Vol.28 (7), p.1670-1676
• Main Authors: PIGNATTI, Patrizia, VIVARELLI, Marina, MEAZZA, Cristina, RIZZOLO, Maria Grazia, MARTINI, Alberto, DE BENEDETTI, Fabrizio
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Adolescent; Arthritis, Juvenile - genetics; Arthritis, Juvenile - immunology; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; Diseases of the osteoarticular system; Humans; Inflammatory joint diseases; Interleukin-10 - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Medical sciences; Polymorphism, Genetic
• ISSN: 0315-162X; 1499-2752

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.