Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis

Objective, To evaluate the in vitro production of interleukin 6 (IL-6) by p eripheral blood mononu clear cells (PBMC) of patients with systemic juvenil e 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 lipopolysaccharid e (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 fragmen t 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 p atients and controls. The -174 G/C polymorphism in the IL-6 gene does not a ppear to be correlated with the high unstimulated IL-6 production or with t he reduced inhibition by IL-10 observed in patients with JIA. No difference s in patients compared to controls and with respect to the published sequen ce were found in the 3 ' untranslated region (UTR) of the IL-6 gene. Conclusion. Most patients with JIA have increased unstimulated production o f IL-6 and reduced inhibition of IL-6 production by IL-10. This abnormal re gulation of IL-6 production is not secondary to a defect in IL-10 productio n, and is not associated with polymorphism of alleles at position -174 of t he 5 ' flanking region or with mutations in the 3 ' untranslated region of the IL-6 gene.