Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis.
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.


CONCLUSIONS
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.
Pignatti
P
P
Clinica Pediatrica dell'Università di Pavia, IRCCS Policlinico San Matteo, Italy.
Vivarelli
M
M
Meazza
C
C
Rizzolo
M G
MG
Martini
A
A
De Benedetti
F
F
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D011110:Polymorphism, Genetic
D020413:3' Untranslated Regions; D015850:Interleukin-6; D016753:Interleukin-10